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 (ALPINE)

A Phase 1b/2 Study of OMP-59R5 in Combination With Nab-Paclitaxel and Gemcitabine in Subjects With Previously Untreated Stage IV Pancreatic Cancer

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.

Study Overview

• Status: Completed
• Conditions: Stage IV Pancreatic Cancer
• Intervention / Treatment: Drug: OMP-59R5; Drug: Placebo; Drug: Gemcitabine; Drug: Nab-Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 217
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Goodyear, Arizona, United States, 85338
      • Western Regional Medical Center, Inc.
  • California
    • Bakersfield, California, United States, 93309
      • CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
    • Fullerton, California, United States, 92835
      • St Jude Heritage Healthcare Virginia K. Crosson Cancer Center
    • Long Beach, California, United States, 90813
      • Pacific Shores Medical Group
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center, Drug Information Center, Department of Pharmaceutical Services
    • Redondo Beach, California, United States, 90277
      • Torrance Health Association Dba Torrance Memorial Physician Network/Cancer Care Associates
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers
  • Florida
    • Orlando, Florida, United States, 32806
      • Orlando Health, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30341
      • Northside Hospital, Inc. - GCS/Almex
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Allina Health, Virginia Piper Cancer Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Comprehensive Cancer Centers ofNevada
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care, Inc.
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Peggy and Charles Stephenson Cancer Center
  • Oregon
    • Bend, Oregon, United States, 97701
      • Bend Memorial Clinic
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System, Clinical Research Unit, Institute for Translational Oncology Research
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Thereapeutics, LLC (START)
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wiscons in Hospi tal and Clinics
    • Milwaukee, Wisconsin, United States, 533226
      • Froedtert Hospital & Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OMP-59R5 plus Gemcitabine and Nab-Paclitaxel	Drug: OMP-59R5; OMP-59R5 administered intravenously; Drug: Gemcitabine; administered intravenously; Drug: Nab-Paclitaxel; administered intravenously; Other Names: Abraxane
Experimental: Gemcitabine and Nab-Paclitaxel plus Placebo	Drug: Placebo; administered IV; Drug: Gemcitabine; administered intravenously; Drug: Nab-Paclitaxel; administered intravenously; Other Names: Abraxane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ib: Number of Participants With Dose-limiting Toxicities (DLT)	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).	Up to 1 year in absence of unacceptable toxicity or disease progression.
Phase 2: Overall Survival (ITT Population)	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.	Up to 1 year in absence of unacceptable toxicity or disease progression.
Phase 2: Median OS by Notch 3 Percentile (ITT Population)	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.	Up to 1 year in absence of unacceptable toxicity or disease progression.

Collaborators and Investigators

• Sponsor: OncoMed Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Hu ZI, Bendell JC, Bullock A, LoConte NK, Hatoum H, Ritch P, Hool H, Leach JW, Sanchez J, Sohal DPS, Strickler J, Patel R, Wang-Gillam A, Firdaus I, Yu KH, Kapoun AM, Holmgren E, Zhou L, Dupont J, Picozzi V, Sahai V, O'Reilly EM. A randomized phase II trial of nab-paclitaxel and gemcitabine with tarextumab or placebo in patients with untreated metastatic pancreatic cancer. Cancer Med. 2019 Sep;8(11):5148-5157. doi: 10.1002/cam4.2425. Epub 2019 Jul 26.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: July 11, 2012
• First Submitted That Met QC Criteria: July 19, 2012
• First Posted (Estimate): July 24, 2012

Study Record Updates

• Last Update Posted (Actual): February 15, 2023
• Last Update Submitted That Met QC Criteria: January 19, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Newly diagnosed Stage IV Pancreatic Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Paclitaxel
• Other Study ID Numbers: 59R5-002