A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Clovis Oncology, Inc.
Sponsor:
Information provided by (Responsible Party):
Clovis Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT01482715
First received: November 22, 2011
Last updated: August 7, 2014
Last verified: August 2014

November 22, 2011
August 7, 2014
November 2011
March 2015   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT01482715 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 ]
Not Provided
Not Provided
 
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

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 the RP2D of oral rucaparib administered daily to patients with a germline BRCA mutation and platinum-sensitive relapsed ovarian cancer.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Peritoneal Cancer
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 until disease progression.
Other Name: CO-338; PF 01367338, AG 14699
Experimental: Oral Rucaparib monotherapy
Intervention: Drug: Rucaparib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
97
Not Provided
March 2015   (final data collection date for primary outcome measure)

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) that has progressed on standard treatment.
  • R2PD Expansion cohort only: Documented deleterious gBRCA mutation.

OR

(PART 2)

  • High-grade epithelial (serous or endometrioid), fallopian tube, or primary peritoneal ovarian cancer associated with a gBRCA mutation that has relapsed >6 mos following prior platinum-based prior treatment and is measurable. Two to four prior treatment regimens permitted.
  • Female

Exclusion Criteria:

(ALL)

  • History of prior malignancy except:

    1. Curatively treated non-melanoma skin cancer
    2. Breast cancer treated curatively >3 years ago, or other solid tumors treated curatively >5 years ago without evidence of recurrence
    3. Synchronous endometrial cancer (Stage IA) 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.
Both
18 Years and older
No
Contact: Clovis Oncology Clinical Trial Information 1-855-262-3040 (USA) clinicaltrialinfo@clovisoncology.com
Contact: Clovis Oncology Clinical Trial Information +1-303-625-5160 (ex-USA) clinicaltrialinfo@clovisoncology.com
United States,   United Kingdom,   Spain,   Canada,   Israel
 
NCT01482715
CO-338-010
No
Clovis Oncology, Inc.
Clovis Oncology, Inc.
Not Provided
Not Provided
Clovis Oncology, Inc.
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP