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

Phase 1

Completed

• Conditions: Stage IV Pancreatic Cancer
• Interventions: Drug: Gemcitabine; Drug: OMP-59R5; Drug: Placebo; Drug: Nab-Paclitaxel

• 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

Study Timeline

• Study First Submitted: 2012-07-11
• Study First Submitted QC: 2012-07-19
• Study First Posted: 2012-07-24
• Study Start: 2012-10
• Primary Completion: 2016-04
• Study Completion: 2016-04
• Results First Submitted: 2018-03-12
• Status Verified: 2023-01
• Results First Submitted QC: 2023-01-19
• Last Update Submitted: 2023-01-19
• Results First Posted: 2023-02-15
• Last Update Posted: 2023-02-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 217

Inclusion Criteria

Subjects must meet all of the following major inclusion criteria to be eligible for the study:

1. 18 years of age or older
2. Histologically or cytologically documented stage IV ductal adenocarcinoma of the pancreas.
3. Performance Status (ECOG) 0 or 1
4. FFPE tumor tissue from metastatic site(s
5. Adequate organ function
6. Written consent on an IRB/IEC-approved Informed Consent Form prior to any study-specific evaluation.
7. 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.
8. 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.

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Exclusion Criteria

Subjects who meet any of the following major exclusion criteria will not be eligible for participation in the study:

1. Neuroendocrine tumors (i.e., carcinoid, islet cell cancer) of the pancreas.
2. Known brain metastases.
3. Prior therapy, including systemic therapy, surgical resection or radiation for newly diagnosed stage IV pancreatic cancer.
4. 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).
5. Any disorder that would significantly compromise protocol compliance.
6. 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.
7. Known human immunodeficiency virus (HIV) infection.
8. Females who are pregnant or breastfeeding.

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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.

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