Description:
Part 1 (Completed Enrollment) - The purpose of the first part of the study was to evaluate
the safety of different doses and dosing regimens of oral rucaparib administered daily to
patients with solid tumors.
Part 2A (Completed Enrollment) and Part 2B (Completed Enrollment) - The purpose of the second
part of the study is to determine the safety and clinical activity of the RP2D of oral
rucaparib administered daily to patients with a known deleterious BRCA mutation (germline or
somatic).
Part 3 (Completed Enrollment) - The purpose of the third part of the study is to further
evaluate PK of higher dose strength tablets at the RP2D in patients with any advanced solid
tumor, inclusive of lymphoma, with evidence of a BRCA mutation (germline or somatic).
Title
- Brief Title: A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II)
- Official Title: A Phase I/II, Open-Label, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Oral Rucaparib in Patients With gBRCA Mutation Ovarian Cancer or Other Solid Tumor
Clinical Trial IDs
- ORG STUDY ID:
CO-338-010
- NCT ID:
NCT01482715
Conditions
- Ovarian Cancer
- Fallopian Tube Cancer
- Peritoneal Cancer
- Advanced Solid Tumor With Evidence of Germline or Somatic BRCA
Interventions
Drug | Synonyms | Arms |
---|
Rucaparib | CO-338; PF 01367338, AG 14699 | Part 1 (Phase 1) |
Purpose
Part 1 (Completed Enrollment) - The purpose of the first part of the study was to evaluate
the safety of different doses and dosing regimens of oral rucaparib administered daily to
patients with solid tumors.
Part 2A (Completed Enrollment) and Part 2B (Completed Enrollment) - The purpose of the second
part of the study is to determine the safety and clinical activity of the RP2D of oral
rucaparib administered daily to patients with a known deleterious BRCA mutation (germline or
somatic).
Part 3 (Completed Enrollment) - The purpose of the third part of the study is to further
evaluate PK of higher dose strength tablets at the RP2D in patients with any advanced solid
tumor, inclusive of lymphoma, with evidence of a BRCA mutation (germline or somatic).
Detailed Description
Rucaparib (CO-338; formerly known as PF 01367338 and AG 14699) is an orally available, small
molecule inhibitor of poly-adenosine diphosphate [ADP] ribose polymerase (PARP) being
developed for treatment of ovarian cancer associated with homologous recombination [HR] DNA
repair deficiency (HRD). The safety and efficacy of rucaparib has been evaluated in several
Phase 1 and Phase 2 studies.
An oral formulation is the focus of current development efforts. Rucaparib is currently being
investigated as monotherapy in patients with cancer associated with BRCA1 or BRCA2 mutations.
For this study, it is anticipated that rucaparib will promote cell death in the
BRCA-deficient tumor cells of ovarian cancer patients with evidence of a germline mutation,
thereby limiting tumor progression and providing therapeutic benefit.
Trial Arms
Name | Type | Description | Interventions |
---|
Part 1 (Phase 1) | Experimental | Rucaparib 40, 80, 160, 300, 500 mg QD and 240, 360, 480, 600, 840 mg BID, for continuous 21-day cycles. Patients in Part 1 were initially treated in a Dose-escalation Evaluation Period (Cycle 1) and could then continue to receive treatment in an optional Treatment-extension Period (Cycle 2 and beyond). | |
Part 2A (Phase 2) | Experimental | Rucaparib 600 mg BID for 21-day cycles. | |
Part 2B (Phase 2) | Experimental | Rucaparib 600 mg BID for 21-day cycles. | |
Part 3 (Phase 2) | Experimental | Rucaparib 600 mg BID for 21-day cycles. Patients also received a single administration of 600 mg rucaparib on both Day -7 and Day 1 for assessing the effect of food on PK. | |
Eligibility Criteria
The following eligibility criteria below pertain to patients enrolling into Part 2B of the
study.
Inclusion Criteria:
- Have a known deleterious BRCA mutation (gBRCA or sBRCA) (as determined by a local
laboratory that has received an international or country-specific, quality standards
certification)
- Have evidence of measurable disease as defined by RECIST Version 1.1
- Have sufficient archival FFPE tumor tissue available for planned analyses. Archival
tissue from the most recently collected biopsy or debulking surgery should be
provided, if available.
- Have a histologically confirmed diagnosis of high-grade epithelial ovarian, fallopian
tube, or primary peritoneal cancer
- Have received at least three prior chemotherapy regimens and have relapsed disease
confirmed by radiologic assessment
Exclusion Criteria:
- 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
- Prior treatment with any PARP inhibitor.
- 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.
- 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 (Grade 2 non-hematologic toxicity to most recent
treatment may be permitted with prior advanced approval from Sponsor).
- Hospitalization for bowel obstruction within 3 months prior to enrollment.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall Response Rate Per RECIST Version 1.1 (Part 2) |
Time Frame: | Time from first dose to date of progression, up to approximately 8 months |
Safety Issue: | |
Description: | The confirmed response rate by RECIST v1.1 is defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR) on subsequent tumor assessment at least 28 days after first response documentation. |
Secondary Outcome Measures
Measure: | Progression-free Survival (PFS) According to RECIST v1.1, as Assessed by the Investigator (Part 2) |
Time Frame: | Cycle 1 Day 1 to End of Treatment, up to approximately 51 months |
Safety Issue: | |
Description: | PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first. |
Measure: | Duration of Response Per RECIST Version 1.1 (Part 2) |
Time Frame: | Cycle 1 Day 1 to End of Treatment, up to approximately 48 months |
Safety Issue: | |
Description: | Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first occurrence of a response until the first occurrence of PD per RECIST. For patients who continued treatment post-progression, the first date of progression was used for the analysis. Any patients with an ongoing response were censored at the date of the last post-baseline scan. |
Measure: | Overall Survival (Part 2B) |
Time Frame: | Cycle 1 Day 1 to date of death, assessed up to 38 months |
Safety Issue: | |
Description: | Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death, due to any cause. Patients without a documented event of death will be censored on the date of their last visit. |
Measure: | Food Effect on PK of Rucaparib - Cmax (Part 1 and Part 3) |
Time Frame: | Day -7 to Cycle 1 Day 1, or approximately 7 days |
Safety Issue: | |
Description: | Cmax = maximum concentration following administration of rucaparib. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted Cmax values were calculated for each arm. |
Measure: | Food Effect on PK of Rucaparib - Tmax (Part 1 and Part 3) |
Time Frame: | Day -7 to Cycle 1 Day 1, or approximately 7 days |
Safety Issue: | |
Description: | Tmax = time to maximum concentration following administration of rucaparib. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted Tmax values were calculated for each arm. |
Measure: | Food Effect on PK of Rucaparib - AUC Last (Part 1 and Part 3) |
Time Frame: | Day -7 to Cycle 1 Day 1, or approximately 7 days |
Safety Issue: | |
Description: | AUC last = Area under the plasma concentration-time curve from time 0 to the last recorded observation. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted AUC last values were calculated for each arm. |
Measure: | QTcF Value Change From Baseline (Part 1) |
Time Frame: | Screening to End of Treatment, up to approximately 15 months |
Safety Issue: | |
Description: | QTcF value change from baseline by daily dose corrected using Fridericia's method (QTcF). To evaluate the effects of rucaparib on the QT (interval from Q wave to T wave)/QTc (interval corrected for heart rate) interval, all patients underwent serial ECG monitoring at Screening, on Cycle 1 Day -1, Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22, on Day 1 of all subsequent cycles, at the EOT Visit, and as clinically indicated. Worst post-baseline QTcF value was used to categorize each patient. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Clovis Oncology, Inc. |
Trial Keywords
- gBRCA ovarian cancer
- platinum sensitive
- PARP Inhibitor
- Rucaparib
- CO-338
- PF 01367338
- AG 14699
- BRCA1
- BRCA2
- platinum sensitive ovarian cancer
- platinum sensitive gBRCA ovarian cancer
- gynecological cancer
- relapsed disease
- homologous recombination deficiency
- HRD
Last Updated
January 22, 2021