A Phase I/II Study of Rucaparib, a PARP Inhibitor, in Patients with gBRCA Mutation Ovarian Cancer, or Other Solid Tumor
- Conditions
- Patients with locally advanced or metastatic solid tumors including lymphoma and germline BRCA (gBRCA) ovarian cancerMedDRA version: 19.0 Level: LLT Classification code 10049280 Term: Solid tumour System Organ Class: 100000004864MedDRA version: 19.0 Level: LLT Classification code 10033130 Term: Ovarian cancer NOS System Organ Class: 100000004864MedDRA version: 19.0 Level: LLT Classification code 10025315 Term: Lymphoma malignant System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-004250-26-GB
- Lead Sponsor
- Clovis Oncology Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- Not specified
- Target Recruitment
- 140
1.Understand and voluntarily sign an 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.Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
4.Have a life expectancy of at least 3 months
5.Have adequate organ function, confirmed by the following laboratory values obtained =14 days prior to the first dose of rucaparib:
-Bone Marrow Function:
-Absolute neutrophil count =1.5 × 10e9/L
-Platelets >100 × 10e9/L
-Hemoglobin =9 g/dL
-Hepatic Function
-Aspartate aminotransferase and alanine aminotransferase =3 × upper limit of normal (ULN); if liver metastases, then =5 × ULN
-Bilirubin =1.5 × ULN (<2 × ULN if hyperbilirubinemia is due to Gilbert's syndrome)
-Serum albumin =30 g/L (3.0 g/dL) (Part 2B only)
-Renal Function
-Serum creatinine =1.5 × ULN
Patients enrolling into Part 1 (Phase I portion) must also meet the following inclusion criteria:
1.Have a histologically or cytologically confirmed solid tumor (lymphoma is included in this category) that is locally recurrent or metastatic and has progressed on standard treatment
2.Have left ventricular ejection fraction > lower level of normal as determined by echocardiogram or multigated acquisition scan evaluation using local institutional standard
3.Be willing and able to eat a high-fat breakfast on Day 1 of the study
4.Have a deleterious gBRCA mutation
All patients enrolling into Part 2 (Phase II portion in OC patients) must also meet the following inclusion criteria:
1.Have a known deleterious BRCA mutation (germline or somatic), as determined by a local laboratory that has received an international or country-specific quality standards certification
2.Have evidence of measurable disease as defined by RECIST Version 1.1
3.Have sufficient archival formalin-fixed paraffin-embedded (FFPE)
tumor tissue available for planned analyses; cytospin blocks from ascites are not acceptable
-Archival tissue from the most recently collected biopsy or debulking surgery should be provided, if available.
Additional inclusion criteria for patients into Part 2A (Phase II portion in OC) include:
1. (b) Have a histologically confirmed diagnosis of high-grade serous or endometrioid
• For mixed histology, >50% of the primary tumor must be confirmed to be high-grade serous or endometrioid upon re-review by local pathology epithelial ovarian, fallopian tube, or primary peritoneal cancer
2. (b) Have received at least two, but no more than four, prior chemotherapy regimens and have relapsed as confirmed by radiologic assessment
a. Last treatment received must have been platinum-based regimen to which patient must have been sensitive (i.e., disease progression occurred at least 6 months after last dose of platinum was administered)
b.A maximum of one non-platinum regimen may have been administered. For patients who received four prior regimens, one regimen must have been a non-platinum
c. Prior
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
2. 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
3.Prior treatment with any PARP inhibitor (Part 1, Part 2). Part 3 patients are permitted to have had previous PARPi, if the following conditions are met:
• PARPi was not the most recent treatment, and
• PARPi was discontinued >6 months before first planned dose of rucaparib
4. In all study parts, patients who previously received iniparib are eligible
5.Untreated or symptomatic central nervous system (CNS) metastases. Patients with asymptomatic CNS metastases are eligible provided they have been clinically stable for at least 4 weeks
6.Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or history of chronic hepatitis B or C.
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.Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib
9.Administration of strong CYP1A2 or CYP3A4 inhibitors =7 days prior to first scheduled dose of rucaparib
10.Non-study related minor surgical procedure =5 days, or major surgical procedure =21 days, prior to first dose of rucaparib; iIn all cases, the patient must be sufficiently recovered and stable before treatment administration.
11.Females who are pregnant or breastfeeding.
12.For fertile patients (female able to become pregnant or male able to father a child), refusal to use effective contraception during the period of the trial and for 6 months after the last dose of rucaparib.
13.Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, psychiatric disturbance, or uncontrolled intercurrent illness including active infection, arterial thrombosis, and symptomatic pulmonary embolism)
14.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.
15.Patients enrolling into Part 1 (Phase I portion) will also be excluded from participation if any of the following criteria apply:
• Family history of long QT syndrome
• Implantable pacemaker or implantable cardioverter defibrillator
• Requires treatment with any medication known to produce QT prolongation, with the excep
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