- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01482715
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
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).
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, MSG 2M9
- Princess Margaret Cancer Centre
-
-
-
-
-
Ramat Gan, Israel, 52621
- Sheba Medical Center
-
Tel Aviv, Israel, 632394
- Tel Aviv Sourasky Medical Center
-
-
-
-
-
Barcelona, Spain, 8035
- Hospital Vall d'Hebron
-
-
-
-
-
London, United Kingdom, WC1E 6BT
- University College London Cancer Institute
-
-
England
-
London, England, United Kingdom, SE1 9RT
- Guy's and St Thomas NHS Foundation Trust
-
London, England, United Kingdom, SW3 6JJ
- Royal Marsden NHS Foundation Trust
-
London, England, United Kingdom, W12 0HS
- Imperial College Healthcare
-
Newcastle Upon Tyne, England, United Kingdom, UK NE7
- Newcastle University
-
-
Scotland
-
Glasgow, Scotland, United Kingdom, G61 1QH
- Institution of Cancer Science, University of Glasgow Wolfson Wohl Cancer Research
-
-
-
-
California
-
San Francisco, California, United States, 94155
- UCSF
-
-
Florida
-
Sarasota, Florida, United States, 34232
- Sarah Cannon Research Institute
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Dana-Farber Cancer Institute (Part 3 only)
-
-
Michigan
-
Detroit, Michigan, United States, 48201
- Karmanos Cancer Institute
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania
-
-
Tennessee
-
Nashville, Tennessee, United States, 37203
- Sarah Cannon Research Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part 1 (Phase 1)
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).
|
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.
Other Names:
|
Experimental: Part 2A (Phase 2)
Rucaparib 600 mg BID for 21-day cycles.
|
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.
Other Names:
|
Experimental: Part 2B (Phase 2)
Rucaparib 600 mg BID for 21-day cycles.
|
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.
Other Names:
|
Experimental: Part 3 (Phase 2)
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.
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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)
Time Frame: Cycle 1 Day 1 to Cycle 1 Day 21
|
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)
Time Frame: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
|
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)
Time Frame: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
|
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)
Time Frame: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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.
|
Cycle 1 Day 1 to End of Treatment, up to approximately 51 months
|
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
|
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.
|
Cycle 1 Day 1 to End of Treatment, up to approximately 48 months
|
Overall Survival (Part 2B)
Time Frame: Cycle 1 Day 1 to date of death, assessed up to 38 months
|
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.
|
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)
Time Frame: Day -7 to Cycle 1 Day 1, or approximately 7 days
|
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.
|
Day -7 to Cycle 1 Day 1, or approximately 7 days
|
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
|
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.
|
Day -7 to Cycle 1 Day 1, or approximately 7 days
|
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
|
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.
|
Day -7 to Cycle 1 Day 1, or approximately 7 days
|
QTcF Value Change From Baseline (Part 1)
Time Frame: Screening to End of Treatment, up to approximately 15 months
|
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.
|
Screening to End of Treatment, up to approximately 15 months
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
General Publications
- Green 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.
- Kristeleit 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.
- Shapiro 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Female
- Endocrine System Diseases
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Endocrine Gland Neoplasms
- Fallopian Tube Diseases
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Ovarian Neoplasms
- Fallopian Tube Neoplasms
- Carcinoma, Ovarian Epithelial
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Poly(ADP-ribose) Polymerase Inhibitors
- Rucaparib
Other Study ID Numbers
- CO-338-010
- 2011-004250-26 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Ovarian Cancer
-
Roswell Park Cancer InstituteCompletedFallopian Tube Carcinoma | Primary Peritoneal Carcinoma | Stage IIA Ovarian Cancer | Stage IIB Ovarian Cancer | Stage IIC Ovarian Cancer | Stage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian Cancer | Stage IA Ovarian Cancer | Stage IB Ovarian Cancer | Stage IC... and other conditionsUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)CompletedCancer Survivor | Stage IIIA Ovarian Epithelial Cancer | Stage IIIB Ovarian Epithelial Cancer | Stage IIIC Ovarian Epithelial Cancer | Stage IIA Ovarian Epithelial Cancer | Stage IIB Ovarian Epithelial Cancer | Stage IIC Ovarian Epithelial Cancer | Stage IA Ovarian Epithelial Cancer | Stage IB Ovarian... and other conditionsUnited States
-
Massachusetts General HospitalJohns Hopkins University; M.D. Anderson Cancer Center; National Cancer Institute... and other collaboratorsRecruitingOvarian Neoplasms | Fallopian Tube Neoplasms | Stage III Ovarian Cancer AJCC v8 | Stage IIIA Ovarian Cancer AJCC v8 | Stage IIIA1 Ovarian Cancer AJCC v8 | Stage IIIA2 Ovarian Cancer AJCC v8 | Stage IIIB Ovarian Cancer AJCC v8 | Stage IIIC Ovarian Cancer AJCC v8 | Stage IV Ovarian Cancer AJCC v8 | Stage... and other conditionsUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedOvarian Clear Cell Cystadenocarcinoma | Ovarian Endometrioid Adenocarcinoma | Ovarian Seromucinous Carcinoma | Ovarian Serous Cystadenocarcinoma | Stage IV Ovarian Germ Cell Tumor | Ovarian Sarcoma | Malignant Ovarian Epithelial Tumor | Ovarian Carcinosarcoma | Ovarian Brenner Tumor | Ovarian Mucinous... and other conditionsUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedStage IIA Fallopian Tube Cancer | Stage IIA Ovarian Cancer | Stage IIB Fallopian Tube Cancer | Stage IIB Ovarian Cancer | Stage IIC Fallopian Tube Cancer | Stage IIC Ovarian Cancer | Stage IIIA Fallopian Tube Cancer | Stage IIIA Ovarian Cancer | Stage IIIA Primary Peritoneal Cancer | Stage IIIB Fallopian... and other conditionsUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedCaregiver | Stage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian CancerUnited States
-
Eve RodlerNot yet recruitingBreast Cancer | Ovarian Cancer | Breast Neoplasm | Breast Carcinoma | Breast Cancer Stage IV | Breast Cancer Stage I | Breast Cancer Stage II | Invasive Breast Cancer | Cancer, Breast | Breast Cancer Stage III | Ovary Cancer | Malignant Tumor of Breast | Ovarian Cancer Stage IIIC | Ovarian Cancer Stage IV | Ovarian Cancer... and other conditionsUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)RecruitingStage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian CancerUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...CompletedStage I Breast Cancer | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage... and other conditionsUnited States
-
University of WashingtonMinnesota Ovarian Cancer AllianceTerminatedStage III Ovarian Cancer AJCC v8 | Stage IIIA Ovarian Cancer AJCC v8 | Stage IIIA1 Ovarian Cancer AJCC v8 | Stage IIIA2 Ovarian Cancer AJCC v8 | Stage IIIB Ovarian Cancer AJCC v8 | Stage IIIC Ovarian Cancer AJCC v8 | Stage IV Ovarian Cancer AJCC v8 | Stage IVA Ovarian Cancer AJCC v8 | Stage IVB Ovarian... and other conditionsUnited States
Clinical Trials on Rucaparib
-
pharmaand GmbHTerminated
-
UNICANCERClovis Oncology, Inc.; Fondation ARCCompletedMetastatic Breast CancerFrance
-
Abramson Cancer Center at Penn MedicineTerminatedPancreatic CancerUnited States
-
zr Pharma & GmbHCompletedNeoplasmsUnited Kingdom, Poland, Slovakia
-
zr Pharma & GmbHFoundation Medicine; Myriad Genetics, Inc.CompletedOvarian Cancer | Fallopian Tube Cancer | Epithelial Ovarian Cancer | Peritoneal CancerUnited States, Spain, Canada, Australia, United Kingdom, France
-
zr Pharma & GmbHCompleted
-
Zhonglin HaoClovis Oncology, Inc.Active, not recruitingSmall Cell Lung CancerUnited States
-
University Hospital, CaenCompleted
-
University Hospital, CaenCompleted
-
Cancer Research UKCompletedBreast Cancer | Ovarian Cancer | brca1 Mutation Carrier | brca2 Mutation CarrierUnited Kingdom