A Phase 1b/2 Study of OMP-59R5 (Tarextumab) in Combination With Nab-Paclitaxel and Gemcitabine in Subjects With Previously Untreated Stage IV Pancreatic Cancer
- Conditions
- Stage IV Pancreatic Cancer
- Interventions
- Registration Number
- NCT01647828
- Lead Sponsor
- OncoMed Pharmaceuticals, Inc.
- Brief Summary
The study consists of a Phase1b lead-in portion to determine the maximum tolerated dose (MTD) of OMP-59R5 in combination with nab-paclitaxel and gemcitabine followed by a Phase 2, multicenter, randomized, placebo-controlled portion to evaluate the efficacy and safety of OMP-59R5 in combination with nab-paclitaxel and gemcitabine in subjects with previously untreated stage IV pancreatic cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 217
Subjects must meet all of the following major inclusion criteria to be eligible for the study:
- 18 years of age or older
- Histologically or cytologically documented stage IV ductal adenocarcinoma of the pancreas.
- Performance Status (ECOG) 0 or 1
- FFPE tumor tissue from metastatic site(s
- Adequate organ function
- Written consent on an IRB/IEC-approved Informed Consent Form prior to any study-specific evaluation.
- For women of child-bearing potential, negative serum pregnancy test at screening and use of physician-approved method of birth control from 30 days prior to the first study drug administration to 30 days following the last study drug administration.
- Male subjects must be surgically sterile or must agree to use physician-approved contraception from 30 days prior to the first study drug administration to 30 days following the last study drug administration.
Subjects who meet any of the following major exclusion criteria will not be eligible for participation in the study:
- Neuroendocrine tumors (i.e., carcinoid, islet cell cancer) of the pancreas.
- Known brain metastases.
- Prior therapy, including systemic therapy, surgical resection or radiation for newly diagnosed stage IV pancreatic cancer.
- Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness including active infection, arterial thrombosis, symptomatic pulmonary embolism).
- Any disorder that would significantly compromise protocol compliance.
- Prior non-pancreatic malignancy treated with chemotherapy. Prior malignancies treated with surgery and/or radiotherapy alone must be in remission ≥3 years. The following prior malignancies are allowable irrespective of when they occurred: in situ carcinoma of the cervix, in situ ductal breast cancer, low-grade local bladder cancer, and nonmelanotic skin cancer.
- Known human immunodeficiency virus (HIV) infection.
- Females who are pregnant or breastfeeding.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Gemcitabine and Nab-Paclitaxel plus Placebo Nab-Paclitaxel Gemcitabine and Nab-Paclitaxel plus Placebo Gemcitabine and Nab-Paclitaxel plus Placebo Gemcitabine Gemcitabine and Nab-Paclitaxel plus Placebo Gemcitabine and Nab-Paclitaxel plus Placebo Placebo Gemcitabine and Nab-Paclitaxel plus Placebo OMP-59R5 plus Gemcitabine and Nab-Paclitaxel OMP-59R5 OMP-59R5 plus Gemcitabine and Nab-Paclitaxel OMP-59R5 plus Gemcitabine and Nab-Paclitaxel Gemcitabine OMP-59R5 plus Gemcitabine and Nab-Paclitaxel OMP-59R5 plus Gemcitabine and Nab-Paclitaxel Nab-Paclitaxel OMP-59R5 plus Gemcitabine and Nab-Paclitaxel
- Primary Outcome Measures
Name Time Method Phase 2: Overall Survival (ITT Population) Up to 1 year in absence of unacceptable toxicity or disease progression. To determine the clinical benefit, as measured by overall survival (OS) ofthe addition of OMP-59R5 to nab-paclitaxel and gemcitabine in all subjects who are receiving first-line therapy for stage IV pancreatic cancer.
Phase Ib: Number of Participants With Dose-limiting Toxicities (DLT) Up to 1 year in absence of unacceptable toxicity or disease progression. Number of participants with dose-limiting toxicities when administered OMP-59R5 every of other week (Days 1 and 15) in combination with nab-paclitaxel (Nab-P) 125 mg/m2 and gemcitabine (Gem) 1000 mg/m2 on Days 1, 8, and 15 of every 28-day cycle in subjects with previously untreated stage IV pancreatic cancer. In the event that no DLTs are observed, maximum tested dose would be considered the Maximum Tolerated Dose (MTD).
Phase 2: Median OS by Notch 3 Percentile (ITT Population) Up to 1 year in absence of unacceptable toxicity or disease progression. To determine the clinical benefit, as measured by OS of the addition of OMP-59R5 to Nab-P+Gem across the 4 subject subsets: subjects with Notch3 ≥ 25th percentile, subjects with Notch3 ≥ 50th percentile, subjects with Notch3 ≥ 75th percentile and all subjects receiving first-line therapy for stage IV pancreatic cancer with Notch3 high expression level.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (26)
CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, California, United States
Ronald Reagan UCLA Medical Center, Drug Information Center, Department of Pharmaceutical Services
🇺🇸Los Angeles, California, United States
Orlando Health, Inc.
🇺🇸Orlando, Florida, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Greenville Health System, Clinical Research Unit, Institute for Translational Oncology Research
🇺🇸Greenville, South Carolina, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Bend Memorial Clinic
🇺🇸Bend, Oregon, United States
University of Wiscons in Hospi tal and Clinics
🇺🇸Madison, Wisconsin, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Allina Health, Virginia Piper Cancer Institute
🇺🇸Minneapolis, Minnesota, United States
Comprehensive Cancer Centers ofNevada
🇺🇸Las Vegas, Nevada, United States
Oncology Hematology Care, Inc.
🇺🇸Cincinnati, Ohio, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Western Regional Medical Center, Inc.
🇺🇸Goodyear, Arizona, United States
St Jude Heritage Healthcare Virginia K. Crosson Cancer Center
🇺🇸Fullerton, California, United States
Pacific Shores Medical Group
🇺🇸Long Beach, California, United States
Torrance Health Association Dba Torrance Memorial Physician Network/Cancer Care Associates
🇺🇸Redondo Beach, California, United States
Northside Hospital, Inc. - GCS/Almex
🇺🇸Atlanta, Georgia, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Peggy and Charles Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
South Texas Accelerated Research Thereapeutics, LLC (START)
🇺🇸San Antonio, Texas, United States
Froedtert Hospital & Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States