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

• Register: EUCTR
• Last refreshed on: 18 October 2021
• Main ID: EUCTR2013-000518-39-DE
• Date of registration: 12/11/2013
• 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: 27/02/2014
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Chief Medical Officer
• Affiliation: Clovis Oncology UK Ltd

• Name: Chief Medical Officer
• 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 (Grade 2 or 3) 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
-Grade 2 tumors classified under a 3-tier system should be re-viewed by local pathology and confimed as high-grade under the 2-tier system
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 chemotherapy regimen is permitted.
-Prior hormonal therapy is permitted; this treatment will not be counted as a non-platinum regimen.
-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 maintenance therapy following a prior treatment regimen is permitted, with the exception of the regimen received immediately prior to maintenance in this study. No anticancer therapy is permitted to be administered as maintenance treatment in the interval period between completion of the most recent PB therapy and initiation of study drug in this trial.
5. Achieved best response of either complete response (CR) or partial response (PR) to the most recent platinum-based regimen administered and is randomized to study treatment within 8 wks of the last dose of platinum received.
The most recent platinum-based regimen must have been a chemotherapy doublet. The choice of the platinum and the 2nd chemotherapy agent is per Investigator' discretion.
A minimum of 4 cycles of platinum chemotherapy must have been administered. There is no cap on the maximum number of cycles; however, additional cycles of treatment administered following completion of therapy for the specific purpose of enabling patient eligibility and randomization within 8 weeks of the last platinum dose is not permitted.
A CR is defined as a complete radiologic response per RECIST v1.1,i.e.absence of any detectable disease and CA-125A PR is defined as either a partial response per RECIST v1.1 (if disease was measurable prior to chemotherapy) or a serologic response per GCIG CA-125 response criteria (if disease was not measurable according to RECIST v1.1).
CA-125 must also be R0 surgery (no visible tumor) or R1 surgery (residual disease <1cm) as a component of the most recent treatment regimen is not permitted. The response assessment must be determined solely in relation to the chemotherapy regimen administered. The presence of measurable disease or CA-125>2xULN immediately prior to the chemotherapy regimen is required.
Responses must have been maintained through the completion of chemotherapy and during the interval period between completio
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. Pre-existing, duodenal stent and / or any other gastrointestinal disorder or defect that would, in the opinion of the Investigator, 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, with the exception of Grade 2 non-hematologic toxicity such as alopecia , peripheral neuropathy and related effects of prior chemotherapy that are likely to be exacerbated by treatment with study drug
-Ongoing hormonal treatment for previously treated breast cancer is permitted
-Refer also to inclusion criteria #4 for guidelines pertaining to prior maintenance therapy
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

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

Platinum-Sensitive, High-Grade Serous or Endometrioid Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer
MedDRA version: 21.0 Level: PT Classification code 10061269 Term: Malignant peritoneal neoplasm System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: PT Classification code 10061328 Term: Ovarian epithelial cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: PT Classification code 10016180 Term: Fallopian tube cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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

Intervention(s)

Trade Name: Rubraca 200 mg film-coated tablets
Product Name: Rucaparib
Product Code: CO-338
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Rucaparib camsylate
CAS Number: 283173-50-2
Current Sponsor code: CO-338
Other descriptive name: RUCAPARIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Rubraca 250 mg film-coated tablets
Product Name: Rucaparib
Product Code: CO-338
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Rucaparib camsylate
CAS Number: 283173-50-2
Current Sponsor code: CO-338
Other descriptive name: RUCAPARIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Rubraca 300 mg film-coated tablets
Product Name: Rucaparib
Product Code: CO-338
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Rucaparib camsylate
CAS Number: 283173-50-2
Current Sponsor code: CO-338
Other descriptive name: RUCAPARIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Disease assessment/tumor scans at the end of every 12 weeks after start of treatment on day 1 of cycle 1.
Patients who have been on study at least 18 months may decrease the frequency of disease assessments to every 16 (±2) weeks.

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

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 Objective: 1.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)
2.To evaluate PRO utilizing the complete FOSI-18
3.To evaluate survival benefit
4. To evaluate PFS by RECIST, as assessed by independent radiology review (IRR), in molecularly-defined HRD subgroups
5.To evaluate safety
6.To determine the population pharmacokinetics (PK) of rucaparib

Secondary Outcome(s)

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

Timepoint(s) of evaluation of this end point: 1. FOSI-18 & EQ-5D instruments are required at Screening, on Day 1 of each treatment cycle, at discontinuation, and at the 28 day posttreatment discontinuation follow-up visit.
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. 3. Every 12 weeks until death, loss to follow-up, withdrawal of consent from study, or closure of the study.
4. As point 3
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 ID(s)

CO-338-014

2013-000518-39-GB

Source(s) of Monetary Support

Clovis Oncology, Inc.

Ethics review

Status: Approved
Approval date: 27/02/2014
Contact:

Results

• Results available: Yes
• Date Posted: 20/05/2021
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000518-39/results