Clinical trial NCT01908478: Veliparib in Combination With Gemcitabine and Intensity Modulated Radiation Therapy in Patients With Pancreatic Cancer
Official title: A Phase I Study of Veliparib (ABT-888) in Combination With Gemcitabine and Intensity Modulated Radiation Therapy in Patients With Locally Advanced, Unresectable Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Cancer
Keywords: locally advanced
unresectable
pancreatic
pancreas
pancreatic adenocarcinoma
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
Collaborators: name: AbbVie
First posted: 2013-07-25
Enrollment: 34
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: This is a Phase I Study of veliparib (ABT-888) in combination with Gemcitabine and Intensity Modulated Radiation Therapy in Patients with Locally Advanced, Unresectable Pancreatic Cancer.

Primary Objectives:

* Determine the maximum tolerable dose of veliparib in combination with gemcitabine and intensity modulated radiation therapy in patients with locally advanced pancreatic cancer.
* Determine the safety and toxicity of the combination of veliparib with gemcitabine and radiation therapy in patients with locally advanced pancreatic cancer

Detailed description: Gemcitabine will be administered by intravenous infusion of 1000 mg/m2 over 30 minutes on days 1, 8, 15 of the cycle. Intensity modulated radiation therapy (IMRT) will be given to a total dose of 36 Gy in 15 fractions (2.4 Gy per fraction, one fraction per day, 5 fractions per week, Monday through Friday) beginning on day 1. Veliparib will be administered per a dose escalation schema. The starting dose of veliparib is 20 mg BID based upon safety/efficacy data available. Dose escalation will continue in 20 mg increments until the maximum tolerated dose (MTD) is reached. Intra-patient dose escalation will not be allowed.

Eligibility criteria: Inclusion Criteria:

* Patients with histopathological or cytological diagnosis of adenocarcinoma of the pancreas, as well as those with high clinical suspicion of adenocarcinoma, which is deemed locally advanced unresectable or borderline resectable as determined by a pancreatic cancer surgeon and/or following evaluation by a GI oncology tumor board.
* Age 18 years or older

Exclusion Criteria:

* Patients who have had prior anti-cancer treatment for their disease
* Patients who are currently receiving any other investigational agents
* Metastatic disease
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to PARP \[Poly (ADP-ribosome) polymerase\] inhibitors or gemcitabine
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Primary outcomes:
measure: Maximum-tolerated dose (MTD) of veliparib based on the incidence of dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)
timeFrame: Days 1-70
Secondary outcomes:
measure: Assessment of objective response rates measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
timeFrame: From baseline to Week 26
measure: Evaluation of pre-treatment biopsy specimens for levels of various DNA repair proteins
timeFrame: Baseline only
measure: Change in PAR [Poly(ADP-ribosyl)ation] levels in peripheral blood mononuclear cells
timeFrame: Baseline, Weekly for 6 weeks, and at Weeks 10, 18, and 26
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Richard Tuli, MD
role: PRINCIPAL_INVESTIGATOR
References: