A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II)
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
2 other identifiers
interventional
136
5 countries
16
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 ovarian-cancer
Started Nov 2011
Longer than P75 for phase_1 ovarian-cancer
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2011
CompletedFirst Submitted
Initial submission to the registry
November 22, 2011
CompletedFirst Posted
Study publicly available on registry
November 30, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2019
CompletedResults Posted
Study results publicly available
December 8, 2020
CompletedJune 9, 2023
June 1, 2023
7.3 years
November 22, 2011
May 16, 2020
June 7, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Overall Response Rate Per RECIST Version 1.1 (Part 2)
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.
Time from first dose to date of progression, up to approximately 8 months
Number of Participants With a Dose Limiting Toxicity (DLT)
The number of Part 1 (Phase 1) patients who experienced dose limiting toxicities after one cycle (21 days) of study drug.
Cycle 1 Day 1 to Cycle 1 Day 21
PK Profile of Rucaparib - Cmax (Part 1)
Cmax = maximum concentration following administration of rucaparib
Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
PK Profile of Rucaparib - Tmax (Part 1)
Tmax = time to maximum concentration following administration of rucaparib
Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
PK Profile of Rucaparib - AUC Last (Part 1)
AUC last = Area under the plasma concentration-time curve from time 0 to the last recorded observation
Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
Secondary Outcomes (7)
Progression-free Survival (PFS) According to RECIST v1.1, as Assessed by the Investigator (Part 2)
Cycle 1 Day 1 to End of Treatment, up to approximately 51 months
Duration of Response Per RECIST Version 1.1 (Part 2)
Cycle 1 Day 1 to End of Treatment, up to approximately 48 months
Overall Survival (Part 2B)
Cycle 1 Day 1 to date of death, assessed up to 38 months
Food Effect on PK of Rucaparib - Cmax (Part 1 and Part 3)
Day -7 to Cycle 1 Day 1, or approximately 7 days
Food Effect on PK of Rucaparib - Tmax (Part 1 and Part 3)
Day -7 to Cycle 1 Day 1, or approximately 7 days
- +2 more secondary outcomes
Study Arms (4)
Part 1 (Phase 1)
EXPERIMENTALRucaparib 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)
EXPERIMENTALRucaparib 600 mg BID for 21-day cycles.
Part 2B (Phase 2)
EXPERIMENTALRucaparib 600 mg BID for 21-day cycles.
Part 3 (Phase 2)
EXPERIMENTALRucaparib 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.
Interventions
Oral tablets administered daily with 8 oz (240 mL) of water on an empty stomach or with food; 21-day cycles of treatment. In Part 1, the initial dose level is 40 mg/day (once a day); doses and dosing frequency(e.g. twice a day or three times a day) will be adjusted until Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) are established. Patients enrolled in Part 2 and Part 3 will receive the RP2D for continuous 21-day treatment cycles until disease progression.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- pharmaand GmbHlead
- Foundation Medicinecollaborator
Study Sites (16)
UCSF
San Francisco, California, 94155, United States
Sarah Cannon Research Institute
Sarasota, Florida, 34232, United States
Dana-Farber Cancer Institute (Part 3 only)
Boston, Massachusetts, 02215, United States
Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Princess Margaret Cancer Centre
Toronto, Ontario, MSG 2M9, Canada
Sheba Medical Center
Ramat Gan, 52621, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 632394, Israel
Hospital Vall d'Hebron
Barcelona, 8035, Spain
Guy's and St Thomas NHS Foundation Trust
London, England, SE1 9RT, United Kingdom
Royal Marsden NHS Foundation Trust
London, England, SW3 6JJ, United Kingdom
Imperial College Healthcare
London, England, W12 0HS, United Kingdom
Newcastle University
Newcastle upon Tyne, England, UK NE7, United Kingdom
Institution of Cancer Science, University of Glasgow Wolfson Wohl Cancer Research
Glasgow, Scotland, G61 1QH, United Kingdom
University College London Cancer Institute
London, WC1E 6BT, United Kingdom
Related Publications (4)
Kristeleit RS, Drew Y, Oza AM, Domchek SM, Banerjee S, Glasspool RM, Balmana J, Chen LM, Patel MR, Burris HA, Safra T, Borrow J, Lin KK, Goble S, Maloney L, Shapira-Frommer R. Efficacy and safety of rucaparib treatment in patients with BRCA-mutated, relapsed ovarian cancer: final results from Study 10. Br J Cancer. 2023 Jan;128(2):255-265. doi: 10.1038/s41416-022-02022-y. Epub 2022 Dec 8.
PMID: 36482193DERIVEDGreen ML, Ma SC, Goble S, Giordano H, Maloney L, Simmons AD, Beltman J, Harding TC, Xiao JJ. Population pharmacokinetics of rucaparib in patients with advanced ovarian cancer or other solid tumors. Cancer Chemother Pharmacol. 2022 May;89(5):671-682. doi: 10.1007/s00280-022-04413-7. Epub 2022 Apr 10.
PMID: 35397664DERIVEDKristeleit RS, Oaknin A, Ray-Coquard I, Leary A, Balmana J, Drew Y, Oza AM, Shapira-Frommer R, Domchek SM, Cameron T, Maloney L, Goble S, Lorusso D, Ledermann JA, McNeish IA. Antitumor activity of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy in patients with platinum-sensitive, relapsed, BRCA-mutated, high-grade ovarian cancer, and an update on safety. Int J Gynecol Cancer. 2019 Nov;29(9):1396-1404. doi: 10.1136/ijgc-2019-000623.
PMID: 31685558DERIVEDShapiro GI, Kristeleit RS, Burris HA, LoRusso P, Patel MR, Drew Y, Giordano H, Maloney L, Watkins S, Goble S, Jaw-Tsai S, Xiao JJ. Pharmacokinetic Study of Rucaparib in Patients With Advanced Solid Tumors. Clin Pharmacol Drug Dev. 2019 Jan;8(1):107-118. doi: 10.1002/cpdd.575. Epub 2018 May 25.
PMID: 29799676DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Information Department
- Organization
- Clovis Oncology, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 22, 2011
First Posted
November 30, 2011
Study Start
November 1, 2011
Primary Completion
March 1, 2019
Study Completion
May 1, 2019
Last Updated
June 9, 2023
Results First Posted
December 8, 2020
Record last verified: 2023-06