Clinical trial NCT02042378: A Study of Rucaparib in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation
Official title: A Phase 2, Open-Label Study of Rucaparib in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma
Keywords: BRCA
BRCA mutation
germline BRCA
somatic BRCA
PARP inhibitor
rucaparib
CO-338
PF 01367338
AG 14699
Clovis
Clovis Oncology
RucaPanc
Lead sponsor: pharmaand GmbH
Sponsor class: INDUSTRY
First posted: 2014-01-22
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Overall Response Rate (ORR) per RECIST v1.1 as assessed by the investigator
timeFrame: Screening, within 7 days prior to the start of every 3rd cycle of treatment, and Treatment Discontinuation Visit. Study to last for ~3 years.
Secondary outcomes:
measure: Overall Response Rate (ORR) per RECIST v1.1 as assessed by independent radiology review
timeFrame: Screening, within 7 days prior to the start of every 3rd cycle of treatment, and Treatment Discontinuation Visit. Study to last for ~3 years.
measure: Duration of Response (DOR) by RECIST v1.1
timeFrame: Screening, within 7 days prior to the start of every 3rd cycle of treatment, and Treatment Discontinuation Visit. Study to last for ~3 years.
measure: PFS defined as the occurrence of disease progression according to RECIST v1.1, as assessed by the investigator, or death from any cause
timeFrame: Screening, within 7 days prior to the start of every 3rd cycle of treatment, and Treatment Discontinuation Visit. Study to last for ~3 years.
measure: Overall Survival (OS)
timeFrame: 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.
measure: Incidence of adverse events (AEs), clinical laboratory abnormalities, and dose modifications
timeFrame: Continuously from signing of informed consent to 28 days after the last dose. Study to last for ~3 years.
measure: Trough (Cmin) level rucaparib concentrations
timeFrame: Cycle 1 Day 15, Cycle 2 Day 15, Cycle 3 Day 1, and Cycle 4 Day 1. Study to last for ~3 years.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: New York University
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Haifa
country: Israel
facility: Rambam Healthcare Campus
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Hospital (Sharett Institute of Oncology)
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
Study officials:
affiliation: Clovis Oncology, Inc.
name: Heidi Giordano
role: STUDY_DIRECTOR
References: