Clinical Trials Register

Summary
EudraCT Number:	2017-004166-10
Sponsor's Protocol Code Number:	CO-338-085
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-04-17
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

Germany - BfArM

A.2

EudraCT number

2017-004166-10

A.3

Full title of the trial

A Phase 2, Open-label Study of Rucaparib in Patients with Locally Advanced or Metastatic Urothelial Carcinoma

A.3.1

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

Study of Rucaparib in Patients with Locally Advanced or Metastatic Urothelial Carcinoma

A.3.2

Name or abbreviated title of the trial where available

ATLAS

A.4.1

Sponsor's protocol code number

CO-338-085

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03397394

A.5.4

Other Identifiers

Name:

US IND

Number:

129840

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 Ireland Limited
B.5.2	Functional name of contact point	Chief Medical Officer
B.5.3	Address:
B.5.3.1	Street Address	Regus Dublin Airport, Skybridge House - Dublin Airport
B.5.3.2	Town/ city	Swords, County Dublin
B.5.3.3	Post code	K67 P6K2
B.5.3.4	Country	Ireland
B.5.4	Telephone number	3531566 5260/1
B.5.5	Fax number	3531566 5208
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 Ireland Limited
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.3.4	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 Ireland Limited
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.3.4	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 Ireland Limited
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.3.4	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

Locally Advanced Unresectable or Metastatic Urothelial Carcinoma

E.1.1.1

Medical condition in easily understood language

bladder 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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10064467
E.1.2	Term	Urothelial carcinoma
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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10044412
E.1.2	Term	Transitional cell carcinoma
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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective for this study is:
• To evaluate objective response rate (ORR) in molecularly-defined homologous recombination deficiency (HRD)-positive and intent-to-treat (ITT) populations using a prospectively defined molecular signature.

E.2.2

Secondary objectives of the trial

The secondary objectives for this study are:
• To evaluate duration of response (DOR)
• To estimate progression-free survival (PFS)
• To estimate overall survival (OS)
• To evaluate safety and tolerability of rucaparib
• To evaluate steady-state pharmacokinetics (PK) of rucaparib

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Have histologically or cytologically confirmed locally advanced unresectable or metastatic transitional cell carcinoma of the urothelium (renal pelvis, ureter, urinary bladder or urethra)
• Received 1 or 2 prior treatment regimens for locally advanced unresectable or metastatic disease and c onfirmed radiologic disease progression during or following recent treatment. The principal investigator is
responsible for ensuring the patient has received standard of care treatment as appropriate in the country of enrollment, taking into account the patient’s current health status as well as how they responded to/tolerated prior treatment(s).
• Mandatory biopsy is required during screening
• Measurable disease per RECIST v1.1
• Adequate organ function
• ECOG 0 or 1

E.4

Principal exclusion criteria

• Prior treatment with a PARP inhibitor
• Symptomatic and/or untreated CNS metastases
• Duodenal stent and/or any gastrointestinal disorder that may interfere with absorption of rucaparib

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint of ORR is defined as a best confirmed response of CR or PR by RECIST v1.1 as assessed by the investigator. The ORR will be summarized with frequencies and percentages for the ITT and HRD-positive populations as well as other HRD subgroups.

E.5.1.1

Timepoint(s) of evaluation of this end point

Tumor assessments will be performed during screening (baseline), at the end of every 8 calendar weeks (±7 days) relative to the first dose of rucaparib (Cycle 1 Day 1) up to 18 months, then every 12 calendar weeks (±7 days), until confirmed radiologic disease progression by RECIST v1.1 criteria, as assessed by the investigator.

E.5.2

Secondary end point(s)

Efficacy:
Duration of Response (DOR):
Duration of confirmed response is defined as the time from the date that a response is first reported to the time that progression is first documented after the confirmed response.

Progression-free Survival (PFS):
PFS will be calculated as 1+ the number of days from the first dose of rucaparib to disease progression or death due to any cause, whichever occurs first.
Patients without a documented event of progression will be censored on the date of their last adequate tumor assessment (ie, radiologic assessment) or date of first dose of rucaparib if no post-baseline tumor assessments have been performed.

Overall Survival (OS):
Overall survival (OS) is defined as the date from first dose of rucaparib to the date of death due to any cause. Patients who have not died will be censored at the date last known to be alive.

Safety:
Safety endpoints include incidence of AEs, clinical laboratory abnormalities, and dose modifications.
Data from all patients in the safety population will be included in the safety analyses. AEs, clinical laboratory results, vital signs, ECG results, ECOG performance status, body weight, and concomitant medications/ procedures will be tabulated and summarized.

PK:
The PK data and selected safety and efficacy endpoints will be included in exploratory population PK and exposure-response analyses, and the results will be reported separately.

E.5.2.1

Timepoint(s) of evaluation of this end point

DOR, PFS, OS please refer to E.5.2

Safety;
The investigator has the responsibility for assessing the safety of the patients and for compliance with the protocol to ensure study integrity. During the screening period, unless otherwise required by local regulations, SAEs which are related to protocol-mandated assessments will be reported. Once enrolled and rucaparib is administered, patients will be monitored for all AEs/SAEs/AESIs during study participation and until 28 days after the last dose of rucaparib. After the 28-day window, only treatment-related SAEs and all AESIs, irrespective of causality, need to be reported.

PK:
Plasma samples are to be collected for trough level PK analysis of rucaparib 1 hour before the morning dose on Cycle 2 Day 1, Cycle 3 Day 1, and Cycle 4 Day 1

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

France

Germany

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

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

120

F.2 Gender

F.2.1

Female

Yes

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

F.4.2.2

In the whole clinical trial

200

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)

Patients will take rucaparib BID for continuous 28-day cycles until disease progression as assessed by the investigator, or other reason for discontinuation.
All patients discontinued from treatment, regardless of reason, will be followed and information collected for subsequent treatments and survival every 12 weeks from last dose of rucaparib until death, loss to follow-up, withdrawal of consent from study, or closure of the study.

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

2018-08-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-09-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-01-15

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