A Study of Rucaparib in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Clovis Oncology, Inc.
Sponsor:
Information provided by (Responsible Party):
Clovis Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT02042378
First received: January 20, 2014
Last updated: September 4, 2014
Last verified: September 2014
  Purpose

The purpose of this study is to determine whether oral rucaparib is effective in the treatment of patients with locally advanced or metastatic pancreatic cancer and a known deleterious BRCA mutation.


Condition Intervention Phase
Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma
Drug: Rucaparib
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 2, Open-Label Study of Rucaparib in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation

Resource links provided by NLM:


Further study details as provided by Clovis Oncology, Inc.:

Primary Outcome Measures:
  • Overall Response Rate (ORR) per RECIST v1.1 as assessed by the investigator [ Time Frame: Screening, within 7 days prior to the start of every 3rd cycle of treatment, and Treatment Discontinuation Visit. Study to last for ~3 years. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall Response Rate (ORR) per RECIST v1.1 as assessed by independent radiology review [ Time Frame: Screening, within 7 days prior to the start of every 3rd cycle of treatment, and Treatment Discontinuation Visit. Study to last for ~3 years. ] [ Designated as safety issue: No ]
  • Duration of Response (DOR) by RECIST v1.1 [ Time Frame: Screening, within 7 days prior to the start of every 3rd cycle of treatment, and Treatment Discontinuation Visit. Study to last for ~3 years. ] [ Designated as safety issue: No ]
  • PFS defined as the occurrence of disease progression according to RECIST v1.1, as assessed by the investigator, or death from any cause [ Time Frame: Screening, within 7 days prior to the start of every 3rd cycle of treatment, and Treatment Discontinuation Visit. Study to last for ~3 years. ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: To be performed continually from first dose of study drug through discontinuation, then every 4 weeks until death, loss to follow-up, withdrawal of consent from study, or closure of the study. Study to last for ~3 years. ] [ Designated as safety issue: No ]
  • Incidence of adverse events (AEs), clinical laboratory abnormalities, and dose modifications [ Time Frame: Continuously from signing of informed consent to 28 days after the last dose. Study to last for ~3 years. ] [ Designated as safety issue: Yes ]
  • Trough (Cmin) level rucaparib concentrations [ Time Frame: Cycle 1 Day 15, Cycle 2 Day 15, Cycle 3 Day 1, and Cycle 4 Day 1. Study to last for ~3 years. ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: April 2014
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rucaparib
All patients will take oral tablets twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.
Drug: Rucaparib
All patients will take oral tablets twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.
Other Names:
  • CO-338
  • PF 01367338
  • AG 14699

Detailed Description:

Rucaparib is an orally available, small molecule inhibitor of poly-adenosine diphosphate [ADP] ribose polymerase (PARP) that inhibits a specific DNA repair pathway known as base excision repair (BER). PARP inhibitors (PARPi) have been shown to effectively kill tumors with a defect in BRCA1 or BRCA2. Clinical benefit has been observed in patients with a gBRCA mutation as well as in those with a somatic BRCA (sBRCA) mutation. Clinical data have also shown that pancreatic cancer patients with a gBRCA mutation benefit from PARPi treatment. Clinical activity of PARP inhibitors in BRCA-mutated pancreatic cancer combined with the paucity of 2nd line therapies support evaluation of rucaparib in pancreatic cancer patients known to harbor a deleterious BRCA mutation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of pancreatic cancer (ductal adenocarcinoma and related subtypes eligible; endocrine and neuroendocrine tumors excluded)
  • Received at least 1, but no more than 2, chemotherapy-based regimens for locally advanced or metastatic disease and has relapsed or progressive disease. Patients no longer able to continue treatment with chemotherapy due to intolerable toxicity may be considered for study participation provided that radiology assessment confirms either stable disease or disease progression (i.e. no response to treatment)
  • Documented deleterious or suspected deleterious (or equivalent interpretation) BRCA mutation (germline or somatic) as assessed by a local laboratory
  • Measurable disease

Exclusion Criteria:

  • Presence of another active cancer
  • Prior treatment with any PARP inhibitor, including rucaparib. Patients treated with prior iniparib are eligible.
  • Symptomatic and/or untreated central nervous system metastases.
  • Clinical evidence of malabsorption and/or any other gastrointestinal disorder or defect that would, in the opinion of the investigator, 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: NCT02042378

Contacts
Contact: Clovis Oncology Clinical Trial Information 1-855-262-3040 (USA) clovistrials@emergingmed.com
Contact: Clovis Oncology Clinical Trial Information +1-303-625-5160 (ex-USA) clovistrials@emergingmed.com

Locations
United States, California
Cedars Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Loni Lee       Loni.Lee@cshs.org   
United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55902
United States, New York
New York University Recruiting
New York, New York, United States, 10012
Contact: Maggie Sidarous       maggie.sidarous@nyumc.org   
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Joanne Ciconte       Joanne.ciconte@uphs.upenn.edu   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Ernesto Harold Booc       ehbooc@mdanderson.org   
Israel
Rambam Healthcare Campus Not yet recruiting
Haifa, Israel, 31096
Hadassah Hebrew University Hospital (Sharett Institute of Oncology) Not yet recruiting
Jerusalem, Israel, 91120
Tel Aviv Sourasky Medical Center Not yet recruiting
Tel Aviv, Israel, 64239
Sponsors and Collaborators
Clovis Oncology, Inc.
Investigators
Study Director: Heidi Giordano Clovis Oncology, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02042378     History of Changes
Other Study ID Numbers: CO-338-023
Study First Received: January 20, 2014
Last Updated: September 4, 2014
Health Authority: United States: Food and Drug Administration
Israel: Ministry of Health

Keywords provided by Clovis Oncology, Inc.:
BRCA
BRCA mutation
germline BRCA
somatic BRCA
PARP inhibitor
rucaparib
CO-338
PF 01367338
AG 14699
Clovis
Clovis Oncology
RucaPanc

Additional relevant MeSH terms:
Pancreatic Neoplasms
Carcinoma, Ductal, Breast
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Neoplasms, Ductal, Lobular, and Medullary
Breast Neoplasms
Breast Diseases
Adenocarcinoma
Carcinoma
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Carcinoma, Ductal
Skin Diseases

ClinicalTrials.gov processed this record on September 18, 2014