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 June 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: June 9, 2014
Last verified: June 2014
  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 the RP2D of oral rucaparib administered daily to patients with a germline BRCA mutation and platinum-sensitive relapsed ovarian cancer.


Condition Intervention Phase
Ovarian Cancer
Fallopian Tube Cancer
Peritoneal 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 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: 97
Study Start Date: November 2011
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral Rucaparib monotherapy 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

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.

  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) 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01482715

Contacts
Contact: Clovis Oncology Clinical Trial Information clinicaltrialinfo@clovisoncology.com

Locations
United States, California
UCSF Not yet recruiting
San Francisco, California, United States, 94155
United States, Florida
Sarah Cannon Research Institute Recruiting
Sarasota, Florida, United States, 34232
Contact: Manish Patel       mpatel@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: Kelly Schneider       schneidk@karmanos.org   
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Susan Domchek       susan.domchek@uphs.upenn.edu   
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Lorie Patterson       lorie.patterson@scresearch.net   
United States, Washington
University of Washington Not yet recruiting
Seattle, Washington, United States, 98109
Canada, Ontario
Princess Margaret Cancer Centre Not yet recruiting
Toronto, Ontario, Canada, MSG 2M9
Israel
Sheba Medical Center Recruiting
Ramat Gan, Israel, 52621
Contact: Hilla Ben Ami       Hilla.BenAmi@sheba.health.gov.il   
Tel Aviv Sourasky Medical Center Recruiting
Tel Aviv, Israel, 632394
Contact: Moshe Inbar       inbr_onc@tasmc.health.gov.il   
Spain
Hospital Vall d'Hebron Recruiting
Barcelona, Spain, 8035
Contact: Elena de Cabo       igrau@vhio.net   
United Kingdom
Sarah Cannon Research Institute UK Recruiting
London, England, United Kingdom, W1G 6AD
Contact       enquiries@sarahcannonresearch.co.uk   
Guy's and St Thomas NHS Foundation Trust Recruiting
London, England, United Kingdom, SE1 9RT
Contact: Anna M Borinaga       ana.montes@gstt.nhs.uk   
Newcastle University Recruiting
Newcastle Upon Tyne, England, United Kingdom, UK NE7
Contact: Ruth Plummer       Ruth.Plummer@newcastle.ac.uk   
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: June 9, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Health Canada
Israel: Ministry of Health
Spain: Ministry of Health

Keywords provided by Clovis Oncology, Inc.:
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

Additional relevant MeSH terms:
Ovarian Neoplasms
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Fallopian Tube Diseases

ClinicalTrials.gov processed this record on July 28, 2014