Download PDF

Clinical Trial Results:
A Phase 2, Open-Label Study of Rucaparib in Patients with Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Summary
EudraCT number	2013-000517-20
Trial protocol	GB ES FR
Global end of trial date

Results information
Results version number	v1(current)
This version publication date	25 Aug 2021
First version publication date	25 Aug 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

CO-338-017

ISRCTN number

US NCT number

NCT01891344

WHO universal trial number (UTN)

Sponsor organisation name

Clovis Oncology UK Ltd

Sponsor organisation address

Granta Centre, Granta Park, Great Abington, Cambridge, United Kingdom, CB21 6GP

Public contact

Dr Lindsey Rolfe, Clovis Oncology UK Ltd, +44 12233645500, lrolfe@clovisoncology.com

Scientific contact

Dr Lindsey Rolfe, Clovis Oncology UK Ltd, +44 12233645500, lrolfe@clovisoncology.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Interim

Date of interim/final analysis

01 Feb 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Main objective of the trial

• To determine progression-free survival (PFS) in patients with relapsed platinum-sensitive ovarian cancer classified into molecularly defined subgroups by a prospectively defined HRD signature (Part 1) • To estimate objective response rate (ORR) in heavily pre-treated patients with relapsed ovarian cancer classified into molecularly-defined subgroups by a prospectively defined HRD signature (Part 2)

Protection of trial subjects

A formal safety data review occurred after the first 20 patients were enrolled, then quarterly until Part 1 of the study was fully enrolled, and then every 6 months thereafter.

Background therapy

Evidence for comparator

Actual start date of recruitment

30 Oct 2013

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

6 Years

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 33

Country: Number of subjects enrolled

United Kingdom: 30

Country: Number of subjects enrolled

France: 71

Country: Number of subjects enrolled

Australia: 27

Country: Number of subjects enrolled

Canada: 137

Country: Number of subjects enrolled

United States: 193

Worldwide total number of subjects

491

EEA total number of subjects

134

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

271

From 65 to 84 years

217

85 years and over

Subject disposition

Top of page

Recruitment details

491 subjects were recruited from 64 sites across 6 countries

Screening details

Part 1 of the study enrolled patients who received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part 1: tBRCA

Arm description

Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor. Part 1 enrolled patients who received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.

Arm type

Experimental

Investigational medicinal product name

Rucaparib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Patients took 600 mg rucaparib orally twice daily (BID) starting on Day 1. Patients took rucaparib BID for continuous 28-day cycles until disease progression as assessed by the investigator, or other reason for discontinuation.

Part 1: Non-tBRCA LOH+

Arm description

Patients without a BRCA mutation in their tumor, but have high LOH (loss of heterozygosity). Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.

Arm type

Experimental

Investigational medicinal product name

Rucaparib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Part 1: Non-tBRCA LOH-

Arm description

Patients without a BRCA mutation in their tumor, but have low LOH. Part 1 enrolled patients received ≥ 1prior platinum-based regimen and had platinum-sensitive disease.

Arm type

Experimental

Investigational medicinal product name

Rucaparib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Part 1: Non-tBRCA LOH Unknown

Arm description

Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s). Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.

Arm type

Experimental

Investigational medicinal product name

Rucaparib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Part 2: tBRCA

Arm description

Patients with a deleterious BRCA mutation detected in their tumor. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Arm type

Experimental

Investigational medicinal product name

Rucaparib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Part 2: Non-tBRCA LOH+

Arm description

Patients without a BRCA mutation in their tumor, but have high LOH. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Arm type

Experimental

Investigational medicinal product name

Rucaparib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Part 2: Non-tBRCA LOH-

Arm description

Patients without a BRCA mutation in their tumor, but have low LOH. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Arm type

Experimental

Investigational medicinal product name

Rucaparib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Part 2: Non-tBRCA LOH Unknown

Arm description

Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s). Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Arm type

Experimental

Investigational medicinal product name

Rucaparib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 1	Part 1: tBRCA	Part 1: Non-tBRCA LOH+	Part 1: Non-tBRCA LOH-	Part 1: Non-tBRCA LOH Unknown	Part 2: tBRCA	Part 2: Non-tBRCA LOH+	Part 2: Non-tBRCA LOH-	Part 2: Non-tBRCA LOH Unknown
Started	40	82	70	12	84	73	107	23
Completed	34	80	70	11	80	72	107	23
Not completed	6	2	0	1	4	1	0	0
Ongoing	6	2	-	1	4	1	-	-

Baseline characteristics

Top of page

Reporting group title

Part 1: tBRCA

Reporting group description

Reporting group title

Part 1: Non-tBRCA LOH+

Reporting group description

Patients without a BRCA mutation in their tumor, but have high LOH (loss of heterozygosity). Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.

Reporting group title

Part 1: Non-tBRCA LOH-

Reporting group description

Patients without a BRCA mutation in their tumor, but have low LOH. Part 1 enrolled patients received ≥ 1prior platinum-based regimen and had platinum-sensitive disease.

Reporting group title

Part 1: Non-tBRCA LOH Unknown

Reporting group description

Reporting group title

Part 2: tBRCA

Reporting group description

Patients with a deleterious BRCA mutation detected in their tumor. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Reporting group title

Part 2: Non-tBRCA LOH+

Reporting group description

Patients without a BRCA mutation in their tumor, but have high LOH. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Reporting group title

Part 2: Non-tBRCA LOH-

Reporting group description

Patients without a BRCA mutation in their tumor, but have low LOH. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Reporting group title

Part 2: Non-tBRCA LOH Unknown

Reporting group description

Reporting group values	Part 1: tBRCA	Part 1: Non-tBRCA LOH+	Part 1: Non-tBRCA LOH-	Part 1: Non-tBRCA LOH Unknown	Part 2: tBRCA	Part 2: Non-tBRCA LOH+	Part 2: Non-tBRCA LOH-	Part 2: Non-tBRCA LOH Unknown	Total
Number of subjects	40	82	70	12	84	73	107	23	491
Age categorical
Units: Subjects
Adults (18-64 years)	24	39	34	5	53	47	56	13	271
From 65-84 years	16	43	35	7	31	26	49	10	217
85 years and over	0	0	1	0	0	0	2	0	3
Age continuous
Units: years
median (full range (min-max))	58.5 (33 to 78)	65 (39 to 83)	65 (31 to 86)	69.5 (44 to 81)	60.5 (41 to 82)	61 (35 to 82)	64 (42 to 91)	62 (43 to 81)	-
Gender categorical
Units: Subjects
Female	40	82	70	12	84	73	107	23	491
Male	0	0	0	0	0	0	0	0	0
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	1	0	0	0	1	0	0	0	2
Asian	3	4	5	1	5	4	5	0	27
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	1	0	1
Black or African American	1	2	1	1	0	1	0	0	6
White	33	67	56	10	59	46	82	18	371
More than one race	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	2	9	8	0	19	22	19	5	84
Platinum Sensitivity Status
Measure Description: Refractory = Best response of progressive disease (PD) and PD occurs during or up to 2 months after regimen; Resistant = PD 0-<6 months after last platinum with best response other than PD; Sensitive = PD ≥6 months after last platinum
Units: Subjects
Refractory	0	0	0	0	12	14	18	4	48
Resistant	0	1	0	1	41	46	56	15	160
Sensitive	40	81	70	11	31	13	33	4	283
Number of Prior Chemotherapy Regimens
Units: Subjects
=0	0	0	0	0	0	0	0	0	0
=1	17	45	47	10	0	0	0	0	119
=2	14	21	16	1	0	1	1	0	54
=3	4	13	6	1	52	44	73	17	210
=4	4	1	0	0	32	28	31	6	102
=5	1	1	1	0	0	0	2	0	5
>5	0	1	0	0	0	0	0	0	1
Number of Prior Platinum Regimens
Units: Subjects
=0	0	0	0	0	0	0	0	0	0
=1	17	45	47	10	2	4	7	3	135
=2	15	25	16	1	34	31	55	7	184
=3	6	10	6	1	40	36	44	12	155
>3	2	2	1	0	8	2	1	1	17

Subject analysis set title

Part 1 Overall

Subject analysis set type

Per protocol

Subject analysis set description

Includes all Part 1 patients

Subject analysis set title

Part 2 Overall

Subject analysis set type

Per protocol

Subject analysis set description

Includes all Part 2 patients

Subject analysis sets values	Part 1 Overall	Part 2 Overall
Number of subjects	204	287
Age categorical
Units: Subjects
Adults (18-64 years)	102	169
From 65-84 years	101	116
85 years and over	1	2
Age continuous
Units: years
median (full range (min-max))
Gender categorical
Units: Subjects
Female
Male
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native
Asian
Native Hawaiian or Other Pacific Islander
Black or African American
White
More than one race
Unknown or Not Reported
Platinum Sensitivity Status
Measure Description: Refractory = Best response of progressive disease (PD) and PD occurs during or up to 2 months after regimen; Resistant = PD 0-<6 months after last platinum with best response other than PD; Sensitive = PD ≥6 months after last platinum
Units: Subjects
Refractory
Resistant
Sensitive
Number of Prior Chemotherapy Regimens
Units: Subjects
=0
=1
=2
=3
=4
=5
>5
Number of Prior Platinum Regimens
Units: Subjects
=0
=1
=2
=3
>3

End points

Top of page

Reporting group title

Part 1: tBRCA

Reporting group description

Reporting group title

Part 1: Non-tBRCA LOH+

Reporting group description

Patients without a BRCA mutation in their tumor, but have high LOH (loss of heterozygosity). Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.

Reporting group title

Part 1: Non-tBRCA LOH-

Reporting group description

Patients without a BRCA mutation in their tumor, but have low LOH. Part 1 enrolled patients received ≥ 1prior platinum-based regimen and had platinum-sensitive disease.

Reporting group title

Part 1: Non-tBRCA LOH Unknown

Reporting group description

Reporting group title

Part 2: tBRCA

Reporting group description

Patients with a deleterious BRCA mutation detected in their tumor. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Reporting group title

Part 2: Non-tBRCA LOH+

Reporting group description

Patients without a BRCA mutation in their tumor, but have high LOH. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Reporting group title

Part 2: Non-tBRCA LOH-

Reporting group description

Patients without a BRCA mutation in their tumor, but have low LOH. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Reporting group title

Part 2: Non-tBRCA LOH Unknown

Reporting group description

Subject analysis set title

Part 1 Overall

Subject analysis set type

Per protocol

Subject analysis set description

Includes all Part 1 patients

Subject analysis set title

Part 2 Overall

Subject analysis set type

Per protocol

Subject analysis set description

Includes all Part 2 patients

Primary: Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD (Homologous Recombination Deficiency) Subgroups (Part 1 of Study)

Top of page

End point title

Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD (Homologous Recombination Deficiency) Subgroups (Part 1 of Study) ^[1]

End point description

The primary efficacy endpoint of PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST (Response Evaluation Criteria in Solid Tumors), as determined by the investigator or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

End point type

Primary

End point timeframe

Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint reports PFS for Part 1 patients only.

End point values	Part 1: tBRCA	Part 1: Non-tBRCA LOH+	Part 1: Non-tBRCA LOH-	Part 1: Non-tBRCA LOH Unknown
Number of subjects analysed	40	82	70	12
Units: Days
median (confidence interval 95%)	388 (273 to 448)	174 (158 to 231)	160 (110 to 188)	223 (55 to 499)

Statistical Analysis 1

Comparison groups

Part 1: tBRCA v Part 1: Non-tBRCA LOH-

Number of subjects included in analysis

110

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Cox proportional hazard

Point estimate

0.273

Confidence interval

level

95%

sides

2-sided

lower limit

0.17

upper limit

0.437

Statistical Analysis 2

Comparison groups

Part 1: Non-tBRCA LOH- v Part 1: Non-tBRCA LOH+

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Cox proportional hazard

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.428

upper limit

0.871

Primary: Objective Response Rate (ORR) by RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)

Top of page

End point title

Objective Response Rate (ORR) by RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study) ^[2] ^[3]

End point description

The confirmed response rate by RECIST v1.1 is defined as the percentage of patients with a confirmed complete response (CR) or partial response (PR) on subsequent tumor assessment at least 28 days after first response documentation. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

End point type

Primary

End point timeframe

Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses was not required for this ORR primary endpoint.
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint reports ORR for Part 2 patients only.

End point values	Part 2: tBRCA	Part 2: Non-tBRCA LOH+	Part 2: Non-tBRCA LOH-	Part 2: Non-tBRCA LOH Unknown
Number of subjects analysed	84	73	107	23
Units: Days
number (confidence interval 95%)	31.0 (21.3 to 42.0)	6.8 (2.3 to 15.3)	5.6 (2.1 to 11.8)	13.0 (2.8 to 33.6)

No statistical analyses for this end point

Secondary: Objective Response Rate (ORR) by RECIST v1.1 (Part 1 of Study)

Top of page

End point title

Objective Response Rate (ORR) by RECIST v1.1 (Part 1 of Study) ^[4]

End point description

The confirmed response rate by RECIST v1.1 is defined as the percentage of patients with a confirmed CR or PR on subsequent tumor assessment at least 28 days after first response documentation. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

End point type

Secondary

End point timeframe

Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint reports ORR for Part 1 patients only.

End point values	Part 1: tBRCA	Part 1: Non-tBRCA LOH+	Part 1: Non-tBRCA LOH-	Part 1: Non-tBRCA LOH Unknown
Number of subjects analysed	40	82	70	12
Units: Percentage of patients
number (confidence interval 95%)	80.0 (64.4 to 90.9)	28.0 (18.7 to 39.1)	10.0 (4.1 to 19.5)	33.3 (9.9 to 65.1)

No statistical analyses for this end point

Secondary: Objective Response Rate (ORR) by RECIST v1.1 and GCIG CA-125 Criteria

Top of page

End point title

Objective Response Rate (ORR) by RECIST v1.1 and GCIG CA-125 Criteria

End point description

The endpoint of ORR defined as the percentage of patients with a best response of CR or PR using RECIST v 1.1 or response per Gynecologic Cancer InterGroup cancer antigen 125 (GCIG CA-125) criteria. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. A response to CA-125 has occurred if there is at least a 50% decrease from baseline: 1. in a sample collected after initiation of study treatment AND 2. that is confirmed in a subsequent sample collected ≥21 days after the prior sample. The absolute value of this confirmatory sample must be ≤110% of the prior sample. The date when the first sample with a 50% decrease from baseline is observed is the date of the CA-125 response.

End point type

Secondary

End point timeframe

Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

End point values	Part 1: tBRCA	Part 1: Non-tBRCA LOH+	Part 1: Non-tBRCA LOH-	Part 1: Non-tBRCA LOH Unknown	Part 2: tBRCA	Part 2: Non-tBRCA LOH+	Part 2: Non-tBRCA LOH-	Part 2: Non-tBRCA LOH Unknown
Number of subjects analysed	40	82	70	12	84	73	107	23
Units: percentage of patients
number (confidence interval 95%)	87.5 (73.2 to 95.8)	46.3 (35.3 to 57.7)	21.4 (12.5 to 32.9)	50.0 (21.1 to 78.9)	54.8 (43.5 to 65.7)	12.3 (5.8 to 22.1)	13.1 (7.3 to 21.0)	30.4 (13.2 to 52.9)

No statistical analyses for this end point

Secondary: Duration of Response Per RECIST v1.1

Top of page

End point title

Duration of Response Per RECIST v1.1

End point description

Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first occurrence of a response until the first occurrence of progressive disease (PD) per RECIST. For patients who continued treatment post-progression, the first date of progression was used for the analysis. Any patients with an ongoing response were censored at the date of the last post-baseline scan. Complete response(CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

End point type

Secondary

End point timeframe

Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

End point values	Part 1: tBRCA	Part 1: Non-tBRCA LOH+	Part 1: Non-tBRCA LOH-	Part 1: Non-tBRCA LOH Unknown	Part 2: tBRCA	Part 2: Non-tBRCA LOH+	Part 2: Non-tBRCA LOH-	Part 2: Non-tBRCA LOH Unknown
Number of subjects analysed	32	23	7	4	26	5	6	3
Units: Days
median (confidence interval 95%)	281 (194 to 393)	329 (174 to 451)	169 (141 to 260)	225 (100 to 1454)	176 (169 to 312)	282 (111 to 1012)	314 (169 to 492)	181 (169 to 224)

No statistical analyses for this end point

Secondary: Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)

Top of page

End point title

Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study) ^[5]

End point description

Progression-Free Survival (PFS) is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

End point type

Secondary

End point timeframe

Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint reports PFS for Part 2 patients only.

End point values	Part 2: tBRCA	Part 2: Non-tBRCA LOH+	Part 2: Non-tBRCA LOH-	Part 2: Non-tBRCA LOH Unknown
Number of subjects analysed	84	73	107	23
Units: Days
median (confidence interval 95%)	223 (188 to 275)	57 (54 to 112)	113 (63 to 165)	110 (56 to 154)

No statistical analyses for this end point

Secondary: Overall Survival (Part 2 of Study)

Top of page

End point title

Overall Survival (Part 2 of Study) ^[6]

End point description

Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death (due to any cause). Patients without a known date of death will be censored on the date the patient was last known to be alive.

End point type

Secondary

End point timeframe

All patients in Part 2 were followed for survival, subsequent therapy, and secondary malignancy every 12 weeks until death, loss to follow-up, withdrawal of consent from study or study closure, whichever happened first, up to 7 years.

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint reports OS for Part 2 patients only.

End point values	Part 2: tBRCA	Part 2: Non-tBRCA LOH+	Part 2: Non-tBRCA LOH-	Part 2: Non-tBRCA LOH Unknown
Number of subjects analysed	84	73	107	23
Units: Months
median (confidence interval 95%)	22.7 (16.7 to 28.6)	14.7 (10.8 to 19.8)	13.3 (9.1 to 16.0)	14.1 (7.4 to 20.1)

No statistical analyses for this end point

Secondary: Steady State Trough (Cmin) Level Rucaparib Concentrations

Top of page

End point title

Steady State Trough (Cmin) Level Rucaparib Concentrations

End point description

Per protocol, the secondary PK endpoint, trough (Cmin) concentrations of rucaparib were summarized with descriptive statistics overall and by cycle in all patients with at least one PK sample collected. Blood samples for trough level PK analysis of rucaparib were drawn at the following timepoints only: on Day 15 of Cycle 1 and on Day 1 of Cycles 2, 3, and 4. Data for other timepoints is not available.

End point type

Secondary

End point timeframe

Cycle 1 Day 15 to Cycle 4 Day 1, or approximately 10 weeks

End point values	Part 1 Overall	Part 2 Overall
Number of subjects analysed	196 ^[7]	267 ^[8]
Units: ng/mL
arithmetic mean (standard deviation)
Cycle 1 Day 15	2020.76 ± 1145.164	2276.37 ± 1587.586
Cycle 2 Day 1	1652.27 ± 935.503	1689.83 ± 1039.953
Cycle 3 Day 1	1557.32 ± 952.903	1552.09 ± 1054.346
Cycle 4 Day 1	1530.41 ± 765.940	1629.14 ± 1026.999

Notes
[7] - C1D15 = 196 patients C2D1 = 186 patients C3D1 = 159 patients C4D1 = 142 patients
[8] - C1D15 = 267 patients C2D1 = 242 patients C3D1 = 174 patients C4D1 = 149 patients

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years.

Adverse event reporting additional description

If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term(system organ class). Adverse Events were monitored/assessed without regard to the subgroups.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.1

Reporting group title

Part 1: Overall

Reporting group description

All patients who participated in Part 1 who received at least one dose of rucaparib

Reporting group title

Part 2: Overall

Reporting group description

All patients who participated in Part 2 who received at least one dose of rucaparib

Serious adverse events	Part 1: Overall	Part 2: Overall
Total subjects affected by serious adverse events
subjects affected / exposed	54 / 204 (26.47%)	92 / 287 (32.06%)
number of deaths (all causes)	2	18
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cancer pain
subjects affected / exposed	0 / 204 (0.00%)	2 / 287 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Malignant neoplasm progression
subjects affected / exposed	11 / 204 (5.39%)	10 / 287 (3.48%)
occurrences causally related to treatment / all	0 / 13	0 / 10
deaths causally related to treatment / all	0 / 1	0 / 8
Metastatic neoplasm
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Myelodysplastic syndrome
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neoplasm malignant
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Vascular disorders
Hypertension
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hypotension
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 204 (0.00%)	4 / 287 (1.39%)
occurrences causally related to treatment / all	1 / 1	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	0 / 204 (0.00%)	7 / 287 (2.44%)
occurrences causally related to treatment / all	0 / 0	1 / 7
deaths causally related to treatment / all	0 / 0	0 / 4
Hyperthermia
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pain
subjects affected / exposed	0 / 204 (0.00%)	2 / 287 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 204 (0.49%)	4 / 287 (1.39%)
occurrences causally related to treatment / all	0 / 1	2 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Vaginal haemorrhage
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	1 / 204 (0.49%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dyspnoea exertional
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemothorax
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	2 / 204 (0.98%)	2 / 287 (0.70%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pleuritic pain
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 204 (0.00%)	2 / 287 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	1 / 204 (0.49%)	3 / 287 (1.05%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1
Psychiatric disorders
Mental status changes
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood cholesterol increased
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood creatinine increased
subjects affected / exposed	1 / 204 (0.49%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemoglobin decreased
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphocyte count decreased
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Neutrophil count decreased
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Transaminases increased
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Weight decreased
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Transfusion reaction
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital, familial and genetic disorders
Long QT syndrome congenital
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pericardial effusion
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Amnesia
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Syncope
subjects affected / exposed	1 / 204 (0.49%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	0 / 204 (0.00%)	2 / 287 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	11 / 204 (5.39%)	12 / 287 (4.18%)
occurrences causally related to treatment / all	12 / 17	9 / 12
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	1 / 204 (0.49%)	6 / 287 (2.09%)
occurrences causally related to treatment / all	1 / 1	5 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Granulocytopenia
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Leukocytosis
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	1 / 204 (0.49%)	2 / 287 (0.70%)
occurrences causally related to treatment / all	0 / 1	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	2 / 204 (0.98%)	2 / 287 (0.70%)
occurrences causally related to treatment / all	2 / 2	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	1 / 204 (0.49%)	6 / 287 (2.09%)
occurrences causally related to treatment / all	0 / 1	2 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ascites
subjects affected / exposed	2 / 204 (0.98%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Constipation
subjects affected / exposed	2 / 204 (0.98%)	3 / 287 (1.05%)
occurrences causally related to treatment / all	1 / 2	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	1 / 204 (0.49%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ileus
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	1 / 204 (0.49%)	6 / 287 (2.09%)
occurrences causally related to treatment / all	0 / 1	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 1
Intestinal perforation
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestinal obstruction
subjects affected / exposed	1 / 204 (0.49%)	2 / 287 (0.70%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Lower gastrointestinal haemorrhage
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nausea
subjects affected / exposed	3 / 204 (1.47%)	7 / 287 (2.44%)
occurrences causally related to treatment / all	1 / 3	11 / 14
deaths causally related to treatment / all	0 / 0	0 / 0
Obstruction gastric
subjects affected / exposed	0 / 204 (0.00%)	2 / 287 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	1 / 204 (0.49%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	11 / 204 (5.39%)	8 / 287 (2.79%)
occurrences causally related to treatment / all	0 / 13	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0
Subileus
subjects affected / exposed	0 / 204 (0.00%)	2 / 287 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 204 (0.49%)	9 / 287 (3.14%)
occurrences causally related to treatment / all	2 / 2	8 / 14
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Bile duct obstruction
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic failure
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic haematoma
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermatomyositis
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	6 / 204 (2.94%)	3 / 287 (1.05%)
occurrences causally related to treatment / all	2 / 7	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Haematuria
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	0 / 204 (0.00%)	2 / 287 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Back pain
subjects affected / exposed	0 / 204 (0.00%)	2 / 287 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Fracture pain
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bacterial pyelonephritis
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Empyema
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lung infection
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphangitis
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	2 / 204 (0.98%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	1 / 204 (0.49%)	2 / 287 (0.70%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	4 / 204 (1.96%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	1 / 5	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Septic shock
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Staphylococcal infection
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	3 / 204 (1.47%)	4 / 287 (1.39%)
occurrences causally related to treatment / all	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 204 (0.00%)	2 / 287 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Dehydration
subjects affected / exposed	1 / 204 (0.49%)	5 / 287 (1.74%)
occurrences causally related to treatment / all	0 / 1	1 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Failure to thrive
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	0 / 204 (0.00%)	1 / 287 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypercholesterolaemia
subjects affected / exposed	1 / 204 (0.49%)	0 / 287 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 204 (0.00%)	2 / 287 (0.70%)
occurrences causally related to treatment / all	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part 1: Overall	Part 2: Overall
Total subjects affected by non serious adverse events
subjects affected / exposed	203 / 204 (99.51%)	285 / 287 (99.30%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	83 / 204 (40.69%)	85 / 287 (29.62%)
occurrences all number	163	161
Aspartate aminotransferase increased
subjects affected / exposed	74 / 204 (36.27%)	92 / 287 (32.06%)
occurrences all number	117	137
Blood alkaline phosphatase increased
subjects affected / exposed	19 / 204 (9.31%)	24 / 287 (8.36%)
occurrences all number	28	31
Blood cholesterol increased
subjects affected / exposed	14 / 204 (6.86%)	13 / 287 (4.53%)
occurrences all number	22	24
Blood creatinine increased
subjects affected / exposed	37 / 204 (18.14%)	65 / 287 (22.65%)
occurrences all number	74	122
Neutrophil count decreased
subjects affected / exposed	20 / 204 (9.80%)	12 / 287 (4.18%)
occurrences all number	53	23
Platelet count decreased
subjects affected / exposed	15 / 204 (7.35%)	36 / 287 (12.54%)
occurrences all number	25	98
Weight decreased
subjects affected / exposed	42 / 204 (20.59%)	30 / 287 (10.45%)
occurrences all number	64	38
White blood cell count decreased
subjects affected / exposed	13 / 204 (6.37%)	12 / 287 (4.18%)
occurrences all number	27	22
Vascular disorders
Hot flush
subjects affected / exposed	15 / 204 (7.35%)	10 / 287 (3.48%)
occurrences all number	15	10
Hypertension
subjects affected / exposed	18 / 204 (8.82%)	12 / 287 (4.18%)
occurrences all number	28	16
Nervous system disorders
Dizziness
subjects affected / exposed	42 / 204 (20.59%)	35 / 287 (12.20%)
occurrences all number	66	43
Dysgeusia
subjects affected / exposed	88 / 204 (43.14%)	93 / 287 (32.40%)
occurrences all number	123	121
Headache
subjects affected / exposed	36 / 204 (17.65%)	35 / 287 (12.20%)
occurrences all number	54	42
Lethargy
subjects affected / exposed	13 / 204 (6.37%)	5 / 287 (1.74%)
occurrences all number	24	7
Neuropathy peripheral
subjects affected / exposed	11 / 204 (5.39%)	11 / 287 (3.83%)
occurrences all number	14	17
Peripheral sensory neuropathy
subjects affected / exposed	11 / 204 (5.39%)	2 / 287 (0.70%)
occurrences all number	20	4
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	73 / 204 (35.78%)	124 / 287 (43.21%)
occurrences all number	306	387
Neutropenia
subjects affected / exposed	13 / 204 (6.37%)	18 / 287 (6.27%)
occurrences all number	26	40
Thrombocytopenia
subjects affected / exposed	24 / 204 (11.76%)	44 / 287 (15.33%)
occurrences all number	37	104
General disorders and administration site conditions
Asthenia
subjects affected / exposed	24 / 204 (11.76%)	68 / 287 (23.69%)
occurrences all number	45	152
Chills
subjects affected / exposed	16 / 204 (7.84%)	8 / 287 (2.79%)
occurrences all number	22	8
Fatigue
subjects affected / exposed	140 / 204 (68.63%)	157 / 287 (54.70%)
occurrences all number	336	357
Influenza like illness
subjects affected / exposed	11 / 204 (5.39%)	6 / 287 (2.09%)
occurrences all number	15	6
Oedema peripheral
subjects affected / exposed	21 / 204 (10.29%)	38 / 287 (13.24%)
occurrences all number	27	48
Pyrexia
subjects affected / exposed	30 / 204 (14.71%)	34 / 287 (11.85%)
occurrences all number	34	42
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	41 / 204 (20.10%)	32 / 287 (11.15%)
occurrences all number	52	40
Abdominal pain
subjects affected / exposed	63 / 204 (30.88%)	93 / 287 (32.40%)
occurrences all number	102	123
Abdominal pain lower
subjects affected / exposed	12 / 204 (5.88%)	12 / 287 (4.18%)
occurrences all number	14	14
Abdominal pain upper
subjects affected / exposed	31 / 204 (15.20%)	36 / 287 (12.54%)
occurrences all number	37	47
Ascites
subjects affected / exposed	13 / 204 (6.37%)	12 / 287 (4.18%)
occurrences all number	24	26
Constipation
subjects affected / exposed	95 / 204 (46.57%)	84 / 287 (29.27%)
occurrences all number	155	104
Diarrhoea
subjects affected / exposed	76 / 204 (37.25%)	84 / 287 (29.27%)
occurrences all number	135	142
Dry mouth
subjects affected / exposed	11 / 204 (5.39%)	12 / 287 (4.18%)
occurrences all number	12	16
Dyspepsia
subjects affected / exposed	24 / 204 (11.76%)	20 / 287 (6.97%)
occurrences all number	28	30
Flatulence
subjects affected / exposed	13 / 204 (6.37%)	7 / 287 (2.44%)
occurrences all number	13	7
Gastrooesophageal reflux disease
subjects affected / exposed	11 / 204 (5.39%)	15 / 287 (5.23%)
occurrences all number	12	19
Nausea
subjects affected / exposed	161 / 204 (78.92%)	219 / 287 (76.31%)
occurrences all number	316	377
Small intestinal obstruction
subjects affected / exposed	12 / 204 (5.88%)	9 / 287 (3.14%)
occurrences all number	18	13
Stomatitis
subjects affected / exposed	25 / 204 (12.25%)	15 / 287 (5.23%)
occurrences all number	45	19
Vomiting
subjects affected / exposed	92 / 204 (45.10%)	126 / 287 (43.90%)
occurrences all number	184	235
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	35 / 204 (17.16%)	30 / 287 (10.45%)
occurrences all number	57	35
Dyspnoea
subjects affected / exposed	46 / 204 (22.55%)	68 / 287 (23.69%)
occurrences all number	62	106
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	22 / 204 (10.78%)	7 / 287 (2.44%)
occurrences all number	24	8
Dry skin
subjects affected / exposed	14 / 204 (6.86%)	6 / 287 (2.09%)
occurrences all number	16	6
Erythema
subjects affected / exposed	7 / 204 (3.43%)	16 / 287 (5.57%)
occurrences all number	8	17
Photosensitivity reaction
subjects affected / exposed	30 / 204 (14.71%)	18 / 287 (6.27%)
occurrences all number	37	19
Pruritus
subjects affected / exposed	20 / 204 (9.80%)	16 / 287 (5.57%)
occurrences all number	25	19
Rash
subjects affected / exposed	21 / 204 (10.29%)	13 / 287 (4.53%)
occurrences all number	26	15
Psychiatric disorders
Anxiety
subjects affected / exposed	14 / 204 (6.86%)	17 / 287 (5.92%)
occurrences all number	17	23
Insomnia
subjects affected / exposed	23 / 204 (11.27%)	30 / 287 (10.45%)
occurrences all number	26	37
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	21 / 204 (10.29%)	20 / 287 (6.97%)
occurrences all number	24	24
Back pain
subjects affected / exposed	33 / 204 (16.18%)	25 / 287 (8.71%)
occurrences all number	43	30
Myalgia
subjects affected / exposed	17 / 204 (8.33%)	15 / 287 (5.23%)
occurrences all number	24	20
Pain in extremity
subjects affected / exposed	21 / 204 (10.29%)	21 / 287 (7.32%)
occurrences all number	30	36
Malignant neoplasm progression
subjects affected / exposed	14 / 204 (6.86%)	14 / 287 (4.88%)
occurrences all number	22	18
Infections and infestations
Nasopharyngitis
subjects affected / exposed	15 / 204 (7.35%)	13 / 287 (4.53%)
occurrences all number	16	24
Upper respiratory tract infection
subjects affected / exposed	27 / 204 (13.24%)	10 / 287 (3.48%)
occurrences all number	31	10
Urinary tract infection
subjects affected / exposed	40 / 204 (19.61%)	36 / 287 (12.54%)
occurrences all number	60	47
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	85 / 204 (41.67%)	112 / 287 (39.02%)
occurrences all number	146	176
Dehydration
subjects affected / exposed	17 / 204 (8.33%)	24 / 287 (8.36%)
occurrences all number	24	38
Hypokalaemia
subjects affected / exposed	17 / 204 (8.33%)	19 / 287 (6.62%)
occurrences all number	22	22
Hypomagnesaemia
subjects affected / exposed	13 / 204 (6.37%)	29 / 287 (10.10%)
occurrences all number	16	45
Hyponatraemia
subjects affected / exposed	7 / 204 (3.43%)	15 / 287 (5.23%)
occurrences all number	11	31

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

19 Aug 2013

•Starting dose was established as 600 mg rucaparib BID. •Language was added to allow a reduction in starting dose if warranted by the data and to clarify dose modification criteria. •Formal safety review added. •Safety language regarding AE management and assessment was added for ALT and AST elevations, and treatment-related AEs. •Language was clarified to reflect that ORR would consist of an integrated assessment of RECIST Version 1.1 and GCIG CA 125 response. •The option of collecting and testing ascites samples was removed.

30 May 2014

•HRD subgroups were revised to include groups with tumor genomic LOH (high or low), as well as BRCA1/2 gene mutation. •The primary objective, and associated endpoint, was changed from efficacy defined by ORR to efficacy as defined by PFS. •Inclusion and exclusion criteria were modified.

19 Dec 2014

•Study design was revised to be a 2-part study. •Specified that the primary endpoint for the heavily pretreated patients enrolled in Part 2 of the study was ORR in molecularly-defined subgroups. •PFS and OS were to be assessed as secondary endpoints. •Inclusion and exclusion criteria were modified. •Additional analytes were added to the required safety laboratory panel to further evaluate the safety profile of rucaparib. • Guidance was added to specify that rucaparib does not have to be held for Grade 3 elevations of ALT/AST if not accompanied by other signs of liver dysfunction. •Added language to specify that patients enrolled into Part 1 and Part 2 would receive 120 and 300/200 mg tablets, respectively, when initiating treatment. •GCIG CA-125 response criteria were modified to only require 1 predose sample. •Changes to statistical analyses •Specified that IRR could be performed as a supportive analysis for all (Part 1 and Part 2) or a subset of patients.

29 Jun 2016

•Study population amended to include parameters to more clearly define women of childbearing potential, and more stringent contraception requirements added. •Modification of dietary restrictions to reflect updated restrictions regarding concomitant use of CYP substrates. •Management guidelines for Grade 3 or Grade 4 ALT/AST elevations provided. •Prior and concomitant therapies revised to reflect updated restrictions on concomitant use of medications that are CYP substrates. •Study procedures updated to specify requirement for serum pregnancy test at each cycle of treatment from Cycle 2 and beyond. •Adverse event management amended to include information pertaining to adverse events of special interest.

17 Jul 2019

•This amendment was to modify the end of study language to clarify that the sponsor could close the study and provide alternatives for patients to continue receiving rucaparib treatment, and to revise the Schedule of Assessments for patients remaining in treatment or follow-up, reducing the number of assessments required at study visits as compared to previously; however, an appropriate level of safety monitoring would remain in place. •An update to decrease the frequency of formal safety reviews to an as needed basis after all patients are enrolled and have been on study at least 6 months or had discontinued prior to 6 months.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
A Phase 2, Open-Label Study of Rucaparib in Patients with Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD (Homologous Recombination Deficiency) Subgroups (Part 1 of Study)

Primary: Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD (Homologous Recombination Deficiency) Subgroups (Part 1 of Study)

Primary: Objective Response Rate (ORR) by RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)

Primary: Objective Response Rate (ORR) by RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)

Secondary: Objective Response Rate (ORR) by RECIST v1.1 (Part 1 of Study)

Secondary: Objective Response Rate (ORR) by RECIST v1.1 (Part 1 of Study)

Secondary: Objective Response Rate (ORR) by RECIST v1.1 and GCIG CA-125 Criteria

Secondary: Objective Response Rate (ORR) by RECIST v1.1 and GCIG CA-125 Criteria

Secondary: Duration of Response Per RECIST v1.1

Secondary: Duration of Response Per RECIST v1.1

Secondary: Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)

Secondary: Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)

Secondary: Overall Survival (Part 2 of Study)

Secondary: Overall Survival (Part 2 of Study)

Secondary: Steady State Trough (Cmin) Level Rucaparib Concentrations

Secondary: Steady State Trough (Cmin) Level Rucaparib Concentrations

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase 2, Open-Label Study of Rucaparib in Patients with Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD (Homologous Recombination Deficiency) Subgroups (Part 1 of Study)

Primary: Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD (Homologous Recombination Deficiency) Subgroups (Part 1 of Study)

Primary: Objective Response Rate (ORR) by RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)

Primary: Objective Response Rate (ORR) by RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)

Secondary: Objective Response Rate (ORR) by RECIST v1.1 (Part 1 of Study)

Secondary: Objective Response Rate (ORR) by RECIST v1.1 (Part 1 of Study)

Secondary: Objective Response Rate (ORR) by RECIST v1.1 and GCIG CA-125 Criteria

Secondary: Objective Response Rate (ORR) by RECIST v1.1 and GCIG CA-125 Criteria

Secondary: Duration of Response Per RECIST v1.1

Secondary: Duration of Response Per RECIST v1.1

Secondary: Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)

Secondary: Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)

Secondary: Overall Survival (Part 2 of Study)

Secondary: Overall Survival (Part 2 of Study)

Secondary: Steady State Trough (Cmin) Level Rucaparib Concentrations

Secondary: Steady State Trough (Cmin) Level Rucaparib Concentrations

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2, Open-Label Study of Rucaparib in Patients with Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer