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: MedDRA version: 20.0 Level: HLT Classification code 10016181 Term: Fallopian tube neoplasms malignant System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal 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)

Registration Number: EUCTR2013-000517-20-GB

Lead Sponsor: Clovis Oncology, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Not specified

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 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
4. Have relapsed/progressive disease as confirmed by radiologic assessment
5. 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.
6. 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 tumour tissue prior to first dose of study drug and had the tumour tissue confirmed by the central laboratory as being of adequate quality (at least 20% tumour content with a minimum of 80% nucleated cellular content)
-If tumour 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 enrolment if archival tumour tissue is provided and deemed of adequate quality. This must occur prior to any treatment with rucaparib.
a. Biopsy must be of solid tumour tissue; ascites is not acceptable.
b. Biopsy must be of sufficient yield for planned analyses.
8. Have sufficient archival formalin-fixed paraffin-embedded (FFPE) tumour tissue available for planned analyses. Cytospin blocks from ascites are not acceptable
- Archival tissue from the initial debulking surgery should be provided, if available. If neoadjuvant treatment was administered, tissue collected prior to such treatment should be provided, if available. If tumour tissue prior to any treatments administered is not available, then the oldest available tumour tissue should be provided.
9. Have measurable disease as defined by RECIST v1.1 in addition to the lesion planned for biopsy; a single RECIST target lesion will suffice if, in the Investigator's opinion, it is of sufficient size that the biopsy will not affect post-dose RECIST evaluations.
10. Have adequate organ function confirmed by the following laboratory values obtained within 14 days prior to the first dose of rucaparib:
a. Bone Marrow Functi

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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 1.To determine PFS in molecularly-defined subgroups identified by a prospectively defined HRD signature;Primary end point(s): 1. Disease progression (RECIST v1.1) as assessed by investigator, or death from any cause in molecularly-defined subgroups identified by a prospectively defined HRD signature;Timepoint(s) of evaluation of this end point: As of implementation of Protocol Amendment 6.1, disease assessment should be performed according to local standard of care per Investigator during and at the end of treatment. ;<br> Secondary Objective: 1. To evaluate the overall response rate (ORR)<br> 2. To estimate ORR including CA-125 response<br> 3. To evaluate duration of response (DOR)<br> 4. To evaluate the safety and tolerability of rucaparib<br> 5. To evaluate the steady state trough level pharmacokinetics (PK) of rucaparib<br>

Secondary Outcome Measures

Name	Time	Method

Related Trials