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

Stage IV Pancreatic Cancer Clinical Trial

— ALPINE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01647828
• Other study ID #: 59R5-002
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 2012
• Est. completion date: April 2016

Study information

• Verified date: January 2023
• Source: Mereo BioPharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 217
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pancreatic Neoplasms
• Stage IV Pancreatic Cancer

Intervention

Drug:
• OMP-59R5
OMP-59R5 administered intravenously
• Gemcitabine
administered intravenously
• Placebo
administered IV
• Nab-Paclitaxel
administered intravenously

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
OncoMed Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.