A Study of Oral Rucaparib in Patients With gBRCA Mutation Breast or Ovarian Cancer, or Other Solid Tumor
This study is currently recruiting participants.
Verified February 2013 by Clovis Oncology, Inc.
Sponsor:
Clovis Oncology, Inc.
Information provided by (Responsible Party):
Clovis Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT01482715
First received: November 22, 2011
Last updated: February 18, 2013
Last verified: February 2013
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Purpose
The purpose of the first part of the study is to evaluate the safety of different doses and dosing regimens of oral rucaparib administered daily to patients with solid tumors.
The purpose of the second part of the study is to determine the safety and clinical activity of oral rucaparib administered daily to patients with a gBRCA mutation and locally advanced or metastatic breast cancer or platinum-sensitive relapsed ovarian cancer.
| Condition | Intervention | Phase |
|---|---|---|
|
Metastatic Solid Tumor Breast Cancer Ovarian Cancer |
Drug: Rucaparib |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I/II, Open-Label, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Oral Rucaparib in Patients With gBRCA Mutation Breast or Ovarian Cancer, or Other Solid Tumor |
Resource links provided by NLM:
Further study details as provided by Clovis Oncology, Inc.:
Primary Outcome Measures:
- Incidence of Grade 3 or 4 adverse events and clinical lab abnormalities defined as DLTs (Part 1) [ Time Frame: Cycle 1 Days 1, 8, 15 and 22 ] [ Designated as safety issue: Yes ]
- PK Profile for Single Dose and at Steady State [ Time Frame: Days 1 and 15 of Cycle 1 ] [ Designated as safety issue: No ]AUC - area under curve from time zero to time t or infinity; Cmax - max concentration; Tmax - time to max concentration; t1/2 - elimination half-life; kel - elimination rate constant; Vss/F - volume of distribution at steady state after nonintravenous administration; Cl/F - total plasma clearance
- Overall Response Rate per RECIST version 1.1 (Part 2) [ Time Frame: Every 2 - 3 cycles of treatment ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- PK profile (fasted and fed) (Part 1 only) [ Time Frame: Day -7 and Day 1 of Cycle 1 ] [ Designated as safety issue: No ]AUC and Cmax
- Change from baseline in QT/QTc interval (ECG) (Part 1 only) [ Time Frame: Every week (Cycle 1); q3wks (Cycles 2+) ] [ Designated as safety issue: Yes ]
- Incidence of AEs, clinical laboratory abnormalities, and ECG abnormalities [ Time Frame: Every 1-2 weeks (Cycle 1); q3wks (Cycles 2+) ] [ Designated as safety issue: Yes ]
- Duration of response per RECIST version 1.1 (Part 2 only) [ Time Frame: Every 2-3 cycles of treatment ] [ Designated as safety issue: No ]
- Response per RECIST version 1.1 (Part 1 only) [ Time Frame: Every 2-3 cycles of treatment ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 137 |
| Study Start Date: | November 2011 |
| Estimated Primary Completion Date: | March 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Rucaparib (Breast Cancer)
Oral rucaparib monotherapy (Part 2 only)
|
Drug: Rucaparib
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 will receive the RP2D for continuous 21-day treatment cycles.
Other Name: CO-338; PF 01367338, AG 14699
|
|
Experimental: Rucaparib (Ovarian Cancer)
Oral rucaparib monotherapy (Part 2 only)
|
Drug: Rucaparib
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 will receive the RP2D for continuous 21-day treatment cycles.
Other Name: CO-338; PF 01367338, AG 14699
|
Detailed Description:
Rucaparib (CO-338; formerly known as PF 01367338 and AG 14699) is a small molecule inhibitor of poly-adenosine disphosphate (ADP) ribose polymerase(PARP) being developed for antitumor therapy as monotherapy and in combination with a variety of chemotherapeutic agents as a chemosensitizer. The safety and efficacy of IV rucaparib administered in combination with chemotherapy has been evaluated in several Phase I and Phase II 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, and in combination with carboplatin in patients with advanced solid tumors. For this study, it is anticipated that rucaparib will promote cell death in the BRCA-deficient tumor cells of breast and ovarian cancer patients with evidence of a germline mutation, thereby limiting tumor progression and providing therapeutic benefit.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
(PART 1)
- All cohorts (Dose Escalation and R2PD expansion): Adequate bone marrow, hepatic (liver), renal, and cardiac function.
- All cohorts: Locally recurrent or metastatic solid tumor (includes lymphoma, all types of breast cancer) that has progressed on standard treatment.
- R2PD Expansion cohort only: Documented deleterious gBRCA mutation.
OR
(PART 2)
- Locally advanced or metastatic breast cancer associated with a gBRCA mutation that has relapsed following prior treatment, is not HER2+, and is measurable. One to three regimens in locally advanced/metastatic setting permitted.
- Ovarian cancer associated with a gBRCA mutation that has relapsed >6 months following platinum-based prior treatment and is measurable. Two to four prior treatment regimens permitted.
Exclusion Criteria:
(ALL)
- History of prior cancer except for non-melanoma skin cancer, curatively treated solid tumor (>5 years ago without evidence of recurrence), and synchronous endometrial cancer (Stage 1A) with ovarian cancer.
- Prior treatment with any PARP inhibitor, including rucaparib. Patients who received prior iniparib are eligible.
- Untreated or symptomatic central nervous system metastases.
- Impaired cardiac function or clinically significant cardiac disease.
- Prior gastrectomy or upper bowel removal or any gastrointestinal disorder that would interfere with the absorption of rucaparib.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01482715
Contacts
| Contact: Clovis Oncology Clinical Trial Information | clinicaltrialinfo@clovisoncology.com |
Locations
| United States, Florida | |
| Sarah Cannon Research Institute | Recruiting |
| Sarasota, Florida, United States, 34232 | |
| Contact: Heather Rieth hrieth@flcancer.com | |
| United States, Massachusetts | |
| Dana-Farber Cancer Institute | Recruiting |
| Boston, Massachusetts, United States, 02215 | |
| Contact: Andrew Wolanski andrew_wolanski@dfci.harvard.edu | |
| United States, Michigan | |
| Karmanos Cancer Institute | Recruiting |
| Detroit, Michigan, United States, 48201 | |
| Contact: Entela Rama ramae@karmanos.org | |
| United States, Tennessee | |
| Sarah Cannon Research Institute | Recruiting |
| Nashville, Tennessee, United States, 37203 | |
| Contact: Julie Pfrommer julie.pfrommer@scresearch.net | |
| United Kingdom | |
| University College London Cancer Institute | Recruiting |
| London, United Kingdom, WC1E 6BT | |
| Contact: Rebecca Kristeleit r.kristeleit@ucl.ac.uk | |
Sponsors and Collaborators
Clovis Oncology, Inc.
More Information
No publications provided
| Responsible Party: | Clovis Oncology, Inc. |
| ClinicalTrials.gov Identifier: | NCT01482715 History of Changes |
| Other Study ID Numbers: | CO-338-010 |
| Study First Received: | November 22, 2011 |
| Last Updated: | February 18, 2013 |
| Health Authority: | United States: Food and Drug Administration United Kingdom: Medicines and Healthcare Products Regulatory Agency |
Keywords provided by Clovis Oncology, Inc.:
|
solid tumor gBRCA breast cancer gBRCA ovarian cancer platinum sensitive PARP Inhibitor Rucaparib CO-338 PF 01367338 |
AG 14699 BRCA1 BRCA2 locally advanced or metastatic solid tumor locally advanced or metastatic gBRCA breast cancer platinum sensitive ovarian cancer platinum sensitive gBRCA ovarian cancer |
Additional relevant MeSH terms:
|
Breast Neoplasms Ovarian Neoplasms Neoplasms Neoplasms by Site Breast Diseases Skin Diseases Endocrine Gland Neoplasms |
Ovarian Diseases Adnexal Diseases Genital Diseases, Female Genital Neoplasms, Female Urogenital Neoplasms Endocrine System Diseases Gonadal Disorders |
ClinicalTrials.gov processed this record on June 18, 2013