Clinical Trials Register

Summary
EudraCT Number:	2016-003162-13
Sponsor's Protocol Code Number:	CO-338-052
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2016-12-22
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2016-003162-13

A.3

Full title of the trial

TRITON2: A Multicenter, Open-label Phase 2 Study of Rucaparib in
Patients with Metastatic Castration-resistant Prostate Cancer Associated
with Homologous Recombination Deficiency

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study to evaluate Rucaparib in patients with metastatic castration-resistant prostate Cancer

A.3.2

Name or abbreviated title of the trial where available

TRITON2

A.4.1

Sponsor's protocol code number

CO-338-052

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02952534

A.5.4

Other Identifiers

Name:

IND

Number:

129,840

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Clovis Oncology, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Clovis Oncology, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Clovis Oncology UK Ltd
B.5.2	Functional name of contact point	Chief Medical Officer
B.5.3	Address:
B.5.3.1	Street Address	Granta Centre, Granta Park, Great Abington
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	CB21 6GP
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44 1223 370 037
B.5.5	Fax number	+441223281 382
B.5.6	E-mail	info@clovisoncology.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Rubraca 200 mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Clovis Oncology UK Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Rucaparib 200mg
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Rucaparib
D.3.9.1	CAS number	283173-50-2
D.3.9.2	Current sponsor code	CO-338
D.3.9.3	Other descriptive name	RUCAPARIB
D.3.9.4	EV Substance Code	SUB74859
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Rubraca 250 mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Clovis Oncology UK Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Rucaparib 250 mg
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Rucaparib
D.3.9.1	CAS number	283173-50-2
D.3.9.2	Current sponsor code	CO-338
D.3.9.3	Other descriptive name	RUCAPARIB
D.3.9.4	EV Substance Code	SUB74859
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Rubraca 300 mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Clovis Oncology UK Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Rucaparib 300 mg
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Rucaparib
D.3.9.1	CAS number	283173-50-2
D.3.9.2	Current sponsor code	CO-338
D.3.9.3	Other descriptive name	RUCAPARIB
D.3.9.4	EV Substance Code	SUB74859
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Metastatic castration-resistant prostate cancer

E.1.1.1

Medical condition in easily understood language

advanced prostate cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10036909
E.1.2	Term	Prostate cancer metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10076506
E.1.2	Term	Castration-resistant prostate cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy of rucaparib based on the response rate in metastatic castration-resistant prostate cancer (mCRPC) patients with homologous recombination deficiency (HRD) who progressed on AR-targeted therapy (abiraterone acetate, enzalutamide, apalutamide or investigational AR-targeted agent) and taxane-based chemotherapy in the castration resistant setting

E.2.2

Secondary objectives of the trial

• To assess duration of response (DOR)
• To assess radiologic PFS (rPFS)
• To assess overall survival (OS)
• To assess clinical benefit rate (CBR)
• To assess PSA response ≥ 50% (all patients)
• To assess PSA response ≥ 90% (all patients)
• To assess time to PSA progression
• To characterize the steady-state pharmacokinetics (PK) of rucaparib in mCRPC patients
• To assess safety and tolerability

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Be 18 years old at the time the informed consent form is signed
2. Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate that is metastatic
3. Be surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL (1.73 nM)
4. Experienced disease progression after having received at least 1 but no more than 2 prior next-generation androgen receptor-targeted therapies and 1 prior taxane-based chemotherapy for castration-resistant disease
5. Have a deleterious mutation in BRCA1/2 or ATM (Cohorts A and B), or molecular evidence of other homologous recombination deficiency (Cohort C)

E.4

Principal exclusion criteria

1. Active second malignancy, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or superficial bladder cancer
2. Prior treatment with any PARP inhibitor, mitoxantrone, cyclophosphamide or any platinum-based chemotherapy
3. Symptomatic and/or untreated central nervous system metastases
4. Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with absorption of rucaparib

E.5 End points

E.5.1

Primary end point(s)

Primary endpoints:
For Cohort A: The primary endpoint is ORR as assessed by central IRR and analyzed separately for patients with deleterious BRCA1/2 and ATM mutations. ORR for Cohort A is defined as the proportion of patients with a confirmed response of CR or PR using modified RECIST Version 1.1 (ie, CR or PR by IRR assessment and no progression in bone per PCWG3 by IRR assessment).

For Cohort B: The primary endpoint is PSA response (≥ 50% decrease) as assessed by a local laboratory and analyzed separately for patients with deleterious BRCA1/2 and ATM mutations. The proportion of patients with ≥ 50% PSA decrease from baseline will be reported.

For Cohort C: The primary endpoint is ORR defined as the proportion of patients with a confirmed response of CR or PR using either modified RECIST Version 1.1 (if measurable visceral and/or nodal disease is present) or ≥ 50% PSA decrease from baseline (if visceral and/or nodal disease is absent). For patients with measurable disease, response will be assessed by central IRR.

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

Secondary endpoints:
- Duration of response is defined as the time from the date that a response (modified RECIST Version 1.1 or PSA ≥ 50%) is first reported to the time that progression (using modified RECIST Version 1.1/PCWG3 criteria or PSA-progression criteria, respectively) is documented.
- Radiologic PFS (rPFS) is defined as the time from first dose of rucaparib to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or death due to any cause, whichever occurs first. Radiologic disease progression includes confirmed bone disease progression and soft tissue disease progression adjudicated by independent central radiological review using the PCWG3 guidelines for bone disease and modified RECIST Version 1.1 for soft tissue disease.
- OS is defined as the date from first dose of rucaparib to the date of death due to any cause.
- CBR is defined as the combination of CR, PR, and SD as defined by modified RECIST Version 1.1 with no progression in bone per PCWG3 criteria. Per RECIST, to be assigned a best overall response of CR or PR, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met.
- Confirmed PSA response is defined as ≥ 50% reduction in PSA from baseline to lowest post-baseline PSA result, with a consecutive assessment conducted at least 3 weeks later. PSA response will be calculated for all patients with PSA values at baseline and at least 1 post-baseline assessment. PSA will be assessed by a local laboratory.
- Time to PSA progression is defined as the time from first dose of rucaparib to the date that a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir (or baseline value for patients who did not have a decline in PSA) in PSA was measured. The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later.

Safety Analyses
Adverse events (AEs), clinical laboratory results, vital signs, ECOG performance status, body weight, and concomitant medications/ procedures will be tabulated and summarized.

E.5.2.1

Timepoint(s) of evaluation of this end point

Tumor assessments by CT/MRI and bone scans will be performed during screening, at the end of every 8 calendar weeks (± 7 days) from Study Day 1 (Week 1) up to 24 weeks and every 12 calendar weeks (± 7 days) thereafter, and at the Treatment Discontinuation Visit, if applicable.

PSA will be measured at Day 1, and then every 28 days and at the treatment Discontinuation Visit.

OS will be monitored until patient death

Safety will be monitored at all visits

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Belgium

Canada

Denmark

France

Germany

Ireland

Israel

Italy

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

144

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

216

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

142

F.4.2.2

In the whole clinical trial

360

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

All patients will continue on standard of care.
Also upon formal closure of the study, individual patients who are continuing to benefit from treatment with rucaparib at the time of study closure, and who do not meet any of the criteria for withdrawal, will have the option of entering an extension protocol in which they can continue to receive rucaparib.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-01-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-02-10

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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