Phase 3 Study of Maintenance Rucaparib in Relapsed High-grade Ovarian Cancer

• Register: EUCTR
• Last refreshed on: 10 March 2014
• Main ID: EUCTR2013-000518-39-ES
• Date of registration: 05/12/2013
• Prospective Registration: Yes
• Primary sponsor: Clovis Oncology, Inc.
• Public title: Phase 3 Study of Maintenance Rucaparib in Relapsed High-grade Ovarian Cancer
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Rucaparib as Switch Maintenance Following Platinum-Based Chemotherapy in Patients with Platinum-Sensitive, High-Grade Serous or Endometrioid Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer - ARIEL 3
• Date of first enrolment: 28/02/2014
• Target sample size: 540
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000518-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Australia, Belgium, Canada, France, Germany, Israel, Italy, New Zealand, Spain, United Kingdom, United States

Contacts

• Name: VP Clinical Development
• Affiliation: Clovis Oncology UK Ltd

• Name: VP Clinical Development
• Affiliation: Clovis Oncology UK Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Have signed an Institutional Review Board/Independent Ethics Committee-approved informed consent form prior to any study-specific evaluation
2. Be ? to 18 years of age at the time the informed consent form is signed
3. Have a histologically confirmed diagnosis of high-grade serous or endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer
-For mixed histology, >50% of the primary tumor must be confirmed to be high-grade serous or endometrioid
4. Received prior platinum based therapy and have platinum sensitive disease (i.e. documented radiologic disease progression >6 months following the last dose of the penultimate platinum administered)
-Received ?2 prior platinum-based treatment regimens, including platinum-based regimen that must have been administered immediately prior to maintenance therapy in this trial. In addition, up to 1 non-platinum is permitted.
-There is no upper limit on the number of prior platinum-based regimens that may have been received, but the patient must have been sensitive to the penultimate platinum-based regimen administered.
-If both neoadjuvant and adjuvant treatment were administered pre/post any debulking surgery, this will be considered 1 treatment regimen
-Prior continuous (e.g. bevacizumab) or switch maintenance therapy following any prior treatment regimen is permitted
5. Achieved best response of either complete response (CR) (defined as complete radiologic response by RECIST) or partial response (PR) (defined as partial response by RECIST and/or a Gynecological Cancer Intergroup Guidelines (GCIG) CA-125 response) to the most recent platinum-based regimen administered (4 cycles minimum) and maintained response through completion of chemotherapy
-All responses require that CA-125 be < upper limit of normal (ULN). Response must have been maintained to permit entry into the study.
-All disease assessments performed prior to and during this chemotherapy regimen must be adequately documented in the patient?s medical record
6. Have sufficient archival formalin-fixed paraffin-embedded (FFPE) tumor tissue (1 x 4 µm section for hematoxylin and eosin [H&E] stain and approximately 8 to 12 x 10 µm sections, or equivalent) available for planned analyses.
-The most recently collected tumor tissue should be provided, if available
-Submission of a tumor block is preferred; if sections are provided, these must all be from the same tumor sample.
-Sample must be received at the central laboratory at least 3 weeks prior to planned start of treatment in order to enable stratification for randomization
7. Have CA-125 measurement 8. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
9. Have adequate organ function confirmed by the following laboratory values obtained within 14 days of the first dose of study drug:
a. Bone Marrow Function
-Absolute neutrophil count (ANC) ?1.5 × 109/L
-Platelets >100 × 109/L
-Hemoglobin ?9 g/dL
b. Hepatic Function
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ?3 × ULN; if liver metastases, then ?5 × ULN
-Bilirubin ?1.5 × ULN
c. Renal Function
-Serum creatinine ?1.5 × ULN or estimated glomerular filtration rate (GFR) ?45 mL/min using the Cockcroft Gault formula
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 405
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 135

Exclusion criteria:
1. History of a prior malignancy except:
a. Curatively treated non-melanoma skin cancer
b. Breast cancer treated curatively >3 years ago, or other solid tumor treated curatively >5 years ago, without evidence of recurrence
c. Synchronous endometrioid endometrial cancer (Stage 1A G1/G2)
2. Prior treatment with any poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, including oral or intravenous rucaparib. Patients who previously received iniparib are eligible.
3. Required drainage of ascites during the final 2 cycles of the last platinum-based regimen and/or during the period between the last dose of chemotherapy of that regimen and randomization to maintenance treatment in this study
4. Symptomatic and/or untreated central nervous system (CNS) metastases. Patients with asymptomatic previously treated CNS metastases are eligible provided they have been clinically stable for at least 4 weeks.
5. Prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with absorption of study drug
6. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or history of chronic hepatitis B or C.
7. Pregnant or breast feeding. Women of childbearing potential must have a negative serum pregnancy test <3 days prior to first dose of study drug
8. Received treatment with chemotherapy, radiation, hormones, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental drugs ?14 days prior to first dose of study drug and/or ongoing adverse effects from such treatment > National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) (NCI CTCAE) Grade 1
9. Received administration of strong CYP1A2 or CYP3A4 inhibitors ?7 days prior to first dose of study drug or have on-going requirements for these medications (Appendix F)
10. Non-study related minor surgical procedure ?5 days, or major surgical procedure ?21 days, prior to first dose of study drug; in all cases, the patient must be sufficiently recovered and stable before treatment administration
11. Presence of any other condition that may increase the risk associated with study participation or interfere with the interpretation of study results, and, in the opinion of the investigator, would make the patient inappropriate for the study

Pregnancy is an exclusion criterion and women of childbearing potential must not be considering getting pregnant during the study.

Patients of reproductive potential must practice an effective method of contraception during treatment and for 6 months following the last study drug dose.

No waivers of these inclusion or exclusion criteria will be granted by the investigator and the sponsor or its designee for any patient enrolled into the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Platinum-Sensitive, High-Grade Serous or Endometrioid Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer
MedDRA version: 14.1 Level: PT Classification code 10061269 Term: Malignant peritoneal neoplasm System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: PT Classification code 10061328 Term: Ovarian epithelial cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: PT Classification code 10016180 Term: Fallopian tube cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: Rucaparib
Product Code: CO-338
Pharmaceutical Form: Tablet
INN or Proposed INN: Rucaparib camsylate
CAS Number: 283173-50-2
Other descriptive name: RUCAPARIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To evaluate progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST), as assessed by the investigator, in molecularly-defined homologous recombination deficiency (HRD) subgroups

Secondary Objective: To evaluate PFS by RECIST, as assessed by independent radiology review (IRR), in molecularly-defined HRD subgroups
To evaluate patient-reported outcome (PRO) of disease-related symptoms utilizing the disease-related symptoms ? physical (DRS?P) subscale of the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) FACT-Ovarian Symptom Index 18 (FOSI-18)
To evaluate PRO utilizing the complete FOSI-18
To evaluate survival benefit
To evaluate safety
To determine the population pharmacokinetics (PK) of rucaparib

Timepoint(s) of evaluation of this end point: Disease assessment/tumor scans at the end of every 3rd cycle of treatment (within 7 days prior to the start of the next cycle)

Primary end point(s): Disease progression according to RECIST Version 1.1 (v1.1), as assessed by the investigator, or death from any cause (invPFS), in molecularly defined subgroups

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Disease assessment/tumor scans at the end of every 3rd cycle of treatment (within 7 days prior to the start of the next cycle)
2. The FOSI-18 and EQ-5D instruments must be completed prior to other scheduled study procedures and dosing (if applicable) at Screening, on Day 1 of each treatment cycle, at treatment discontinuation, and at the 28-day post-treatment discontinuation follow-up visit for all patients
3. As point 2.
4. Every 12 weeks until death, loss to follow-up, withdrawal of consent from study, or closure of the study.
5. AEs that occur after first dose through to 28 days after last dose of study drug will be recorded
6. Day 15 of Cycle 1, on Day 1 of Cycle 2, on Day 15 of Cycle 2, and on Day 1 of Cycle 4 and Cycle 7.

Secondary end point(s): 1. Disease progression according to RECIST v1.1, as assessed by independent radiology review(IRR), or death from any cause (irrPFS), in molecularly defined subgroups
2. Time to a 4-point decrease in the disease-related symptoms physical (DSR-P subscale) of the FACT-Ovarian Symptom Index 18 (FOSI-18)
3. Time to an 8-point decrease in the total score of the FOSI-18
4. Overall Survival (OS)
5. Incidence of AEs, clinical laboratory abnormalities, and dose modifications
6. Individual model parameter estimates of rucaparib and covariates identification

Secondary ID(s)

2013-000518-39-GB

CO-338-014

Source(s) of Monetary Support

Clovis Oncology, Inc.