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

Phase 1

Conditions: Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
MedDRA version: 20.0Level: PTClassification code 10061269Term: Malignant peritoneal neoplasmSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: HLTClassification code 10016181Term: Fallopian tube neoplasms malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-000517-20-FR

Lead Sponsor: Clovis Oncology, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 500

Inclusion Criteria

1. Have signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form prior to any study-specific evaluation
2. Be =18 years of age at the time the informed consent form is signed
3. Have a histologically confirmed diagnosis of high-grade serous or Grade 2 or Grade 3 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer
- If mixed histology, >50% of the primary tumor must be confirmed to be high-grade serous or endometrioid upon re-review by local pathology
- Patients with a histology other than serous or endometrioid are also eligible for Part 2 of the study if they are known to harbor a deleterious/pathogenic BRCA mutation (germline or somatic)
4. Have relapsed/progressive disease as confirmed by radiologic assessment
5. Part 1: Received prior platinum-based therapy and have platinum-sensitive disease
a. Received =1 prior platinum-based treatment regimen; AND
b. Received a platinum-based regimen as their last treatment; continuous or switch maintenance treatment as part of this regimen is permitted (hormonal treatment may be permitted following the last platinum regimen with advance approval from the Sponsor); AND
c. Was sensitive to the last platinum regimen. Platinum-sensitive disease is defined as documented radiologic progression =6 months after the last dose of platinum administered in the treatment setting.
Part 2: Received at least 3, but no more than 4, prior chemotherapy
regimens and had documented treatment-free interval of =6 months
following 1st chemotherapy regimen received
a.Hormonal agents (eg. tamoxifen, letrozole, etc), anti-angiogenic
agents (eg. bevacizumab, pazopanib, cediranib, nintedanib, trebananib, etc), and other non-chemotherapy agents administered as single agent treatement will not be counted as a chemotherapy regimen for the purpose of determing patient eligibility
b.Agents administered in the maintenance setting will not be counted as a separate regimen
6. Part 1 only: If <55 years of age at diagnosis, or has prior history of breast cancer, or has close relative (first or second degree) with ovarian cancer or early onset (7. Have undergone a biopsy of tumor tissue prior to first dose of study drug and had the tumor tissue confirmed by the central laboratory as being of adequate quality
(at least 20% tumor content with a minimum of 80% nucleated cellular content). Note: biopsy is optional for Part 2 patients known to harbor a deleterious gBRCA mutation.
- If tumor tissue obtained from the biopsy is deemed inadequate, and the patient is unwilling or unable to have another biopsy, the patient may be considered for enrollment if archival tumor tissue is provided and deemed of adequate quality. This must occur prior to any treatment with rucaparib.
a. Biopsy must be of solid tumor tissue; ascites is not acceptable.
b. Biopsy must be of sufficient yield for planned analyses.
8. Have sufficient archival FFPE tumor tissue available for planned
analyses; cytospin blocks from ascites are not acceptable.
- ? The most recently obtained tumor tissue that is of adequate quality (at least 20% tumor content with a minimum of 80% nucleated cellular content) should be submitted
9. Have measurable disease as defined by RECIST v1.1 in additio

Exclusion Criteria

1. Active second malignancy, i.e., patient known to have potentially fatal cancer present for which she may be (but not necessarily) currently receiving treatment
a. Patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial provided all chemotherapy was completed >6 months prior and/or bone marrow transplant (BMT) >2 years prior to first dose of rucaparib
2. Prior treatment with any PARP inhibitor, including oral or intravenous rucaparib. Patients who previously received iniparib are eligible
3. 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
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
5. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or history of chronic hepatitis B or C
6. Pregnant or breast feeding. Women of childbearing potential must have a negative serum pregnancy test <3 days prior to first dose of rucaparib.
7. Received treatment with chemotherapy, radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental drugs =14 days prior to first dose of rucaparib and/or ongoing adverse effects from such treatment > NCI CTCAE Grade 1 (ongoing Grade 2 non-hematologic toxicity related to most recent treatment regimen may be permitted with prior advanced approval from Sponsor).
8. Received administration of strong CYP1A2 or CYP3A4 inhibitors =7 days prior to first dose of rucaparib or have on-going requirements for these medications
9. Non-study related minor surgical procedure =5 days, or major surgical procedure =21
days, prior to first dose of rucaparib; in all cases, the patient must be sufficiently recovered and stable before treatment administration
10. Presence of any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results, and, in the opinion of the investigator, would make the patient inappropriate for entry into the study
11.Diagnosis of low-grade serous or Grade 1 endometrioid ovarian
cancer
12.Part 2 Only: Hospitalization for bowel obstruction within 3 months
prior to enrollment

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Related Trials