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Study of Gemcitabine, Abraxane® Plus Placebo Versus Gemcitabine, Abraxane® Plus 1 or 2 Truncated Courses of Demcizumab in Subjects With 1st-Line Metastatic Pancreatic Ductal Adenocarcinoma

Phase 2
Completed
Conditions
Pancreatic Cancer
Interventions
Registration Number
NCT02289898
Lead Sponsor
OncoMed Pharmaceuticals, Inc.
Brief Summary

This is a randomized, double blind, 3 arm (1:1:1) study in subjects with 1st-line metastatic pancreatic ductal adenocarcinoma.

The purpose is to test the efficacy and safety of demcizumab, when given in combination with gemcitabine and Abraxane® compared to placebo. The administration of gemcitabine and Abraxane® is a standard treatment for patients with metastatic pancreatic ductal adenocarcinoma.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
207
Inclusion Criteria
  1. Subjects must have histologically confirmed metastatic pancreatic ductal adenocarcinoma.. Prior chemotherapy and/or radiotherapy either in the adjuvant or neoadjuvant setting or for metastatic disease is not allowed.
  2. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue (from either the primary tumor, locoregional disease or a metastatic site), either fresh core-needle-biopsied or archived (two FFPE cores preferred whenever possible). If fresh tissue is obtained, the core biopsy must be done at least 7 days prior to randomization.
  3. Age ≥21 years
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 5. Measurable disease per RECIST v1.1
  5. Adequate organ and marrow function
  6. Signed Informed Consent Form
  7. For women of childbearing potential, agreement to use two effective forms of contraception
Exclusion Criteria
  1. Subjects with a neuroendocrine tumor of the pancreas, an acinar tumor of the pancreas or a pancreatic tumor with mixed histologies.
  2. Subjects receiving heparin, warfarin, factor Xa inhibitors or other similar anticoagulants. Note: Subjects may be receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents.
  3. Subjects with brain metastases, leptomeningeal disease, uncontrolled seizure disorder, or active neurologic disease
  4. Subjects with Grade >2 peripheral neuropathy
  5. Subjects with clinically significant ascites
  6. Malignancies other than pancreatic cancer successfully treated within 3 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, treated superficial bladder cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent
  7. Significant intercurrent illness that will limit the patient's ability to participate in the study or may result in their death over the next 18 months
  8. History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy
  9. Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease
  10. Pregnant women or nursing women
  11. Subjects with known HIV infection
  12. Known bleeding disorder or coagulopathy

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Abraxane® and gemcitabine plus placeboAbraxane®Abraxane® and gemcitabine plus placebo (3 cycles), Abraxane® and gemcitabine (3 cycles), Abraxane® and gemcitabine plus placebo (3 cycles) and then Abraxane® and gemcitabine until disease progression
Abraxane® and gemcitabine plus demcizumab plus placeboAbraxane®Abraxane® and gemcitabine plus demcizumab (3 cycles), Abraxane® and gemcitabine (3 cycles), Abraxane® and gemcitabine plus placebo (3 cycles) and then Abraxane® and gemcitabine until disease progression
Abraxane® and gemcitabine plus demcizumabAbraxane®Abraxane® and gemcitabine plus demcizumab (3 cycles), Abraxane® and gemcitabine (3 cycles), Abraxane® and gemcitabine plus demcizumab (3 cycles) and then Abraxane® and gemcitabine until disease progression
Abraxane® and gemcitabine plus placeboPlaceboAbraxane® and gemcitabine plus placebo (3 cycles), Abraxane® and gemcitabine (3 cycles), Abraxane® and gemcitabine plus placebo (3 cycles) and then Abraxane® and gemcitabine until disease progression
Abraxane® and gemcitabine plus placebogemcitabineAbraxane® and gemcitabine plus placebo (3 cycles), Abraxane® and gemcitabine (3 cycles), Abraxane® and gemcitabine plus placebo (3 cycles) and then Abraxane® and gemcitabine until disease progression
Abraxane® and gemcitabine plus placeboDemcizumabAbraxane® and gemcitabine plus placebo (3 cycles), Abraxane® and gemcitabine (3 cycles), Abraxane® and gemcitabine plus placebo (3 cycles) and then Abraxane® and gemcitabine until disease progression
Abraxane® and gemcitabine plus demcizumab plus placebogemcitabineAbraxane® and gemcitabine plus demcizumab (3 cycles), Abraxane® and gemcitabine (3 cycles), Abraxane® and gemcitabine plus placebo (3 cycles) and then Abraxane® and gemcitabine until disease progression
Abraxane® and gemcitabine plus demcizumabgemcitabineAbraxane® and gemcitabine plus demcizumab (3 cycles), Abraxane® and gemcitabine (3 cycles), Abraxane® and gemcitabine plus demcizumab (3 cycles) and then Abraxane® and gemcitabine until disease progression
Abraxane® and gemcitabine plus demcizumabDemcizumabAbraxane® and gemcitabine plus demcizumab (3 cycles), Abraxane® and gemcitabine (3 cycles), Abraxane® and gemcitabine plus demcizumab (3 cycles) and then Abraxane® and gemcitabine until disease progression
Abraxane® and gemcitabine plus demcizumab plus placeboDemcizumabAbraxane® and gemcitabine plus demcizumab (3 cycles), Abraxane® and gemcitabine (3 cycles), Abraxane® and gemcitabine plus placebo (3 cycles) and then Abraxane® and gemcitabine until disease progression
Primary Outcome Measures
NameTimeMethod
Hazard of Progression in the Placebo/Placebo Arm and the Pooled Demcizumab ArmsInvestigator-assessed progression-free survival time through duration of the study (2 years, 23 days).

Investigator assessed Kaplan-Meier estimates of progression-free survival for placebo/placebo arm and pooled demcizumab arm.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (41)

Lynn Cancer Institute

🇺🇸

Boca Raton, Florida, United States

University of Kansas Cancer Center

🇺🇸

Westwood, Kansas, United States

St John of God Murdoch Hospital

🇦🇺

Murdoch, Western Australia, Australia

St. John of God Subiaco Hospital

🇦🇺

Subiaco, Western Australia, Australia

Ochsner Clinic Foundation

🇺🇸

New Orleans, Louisiana, United States

City of Hope

🇺🇸

Duarte, California, United States

Providence Saint Joseph Medical Center

🇺🇸

Burbank, California, United States

Scripps Cancer Center

🇺🇸

La Jolla, California, United States

University of California, Davis Comprehensive Cancer Center

🇺🇸

Sacramento, California, United States

Kaiser Permanente Medical Center

🇺🇸

Vallejo, California, United States

University of Iowa Hospitals and Clinics

🇺🇸

Iowa City, Iowa, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center

🇺🇸

Lebanon, New Hampshire, United States

University of Rochester

🇺🇸

Rochester, New York, United States

SUNY Upstate Medical University

🇺🇸

Syracuse, New York, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Joe Arrington Cancer Research Treatment Center

🇺🇸

Lubbock, Texas, United States

Thomas Jefferson University, Sydney Kimmel Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

Prince of Wales Hospital

🇦🇺

Randwick, New South Wales, Australia

Western Health (Sunshine Hospitals)

🇦🇺

St Albans, Victoria, Australia

British Columbia Cancer Agency

🇨🇦

Vancouver, British Columbia, Canada

St Josephs Health Centre

🇨🇦

Toronto, Ontario, Canada

London Regional Cancer Program

🇨🇦

London, Ontario, Canada

Sunnybrook Health Sciences Centre, Odette Cancer Centre

🇨🇦

Toronto, Ontario, Canada

Princess Margaret Hospital

🇨🇦

Toronto, Ontario, Canada

Hospital Universitario de Fuenlabrada

🇪🇸

Madrid, Spain

Hospital Universitari Germans Trias i Pujol - lnstituto Catalan d'Oncologia (!CO)

🇪🇸

Barcelona, Spain

Hospital Universitario Miguel Servet

🇪🇸

Zaragoza, Spain

Hospital General Universitario Gregorio Marafi6n

🇪🇸

Madrid, Spain

Bristol Haematology & Oncology Centre

🇬🇧

Bristol, United Kingdom

Sarah Cannon Research Institute UK

🇬🇧

London, United Kingdom

Banner MD Anderson Cancer Center

🇺🇸

Gilbert, Arizona, United States

Monash Medical Centre, Moorabbin

🇦🇺

Bentleigh East, Victoria, Australia

Hopital Erasme

🇧🇪

Brussels, Brussels Capital, Belgium

Tom Baker Cancer Centre

🇨🇦

Calgary, Alberta, Canada

QEII Health Sciences Centre

🇨🇦

Halifax, Nova Scotia, Canada

Rocky Mountain Cancer Centers

🇺🇸

Denver, Colorado, United States

Huntsman Cancer Institute at The University of Utah

🇺🇸

Salt Lake City, Utah, United States

Kaiser Permanente NW Oncology Research

🇺🇸

Portland, Oregon, United States

Soulhern California Permanente Medical Group

🇺🇸

San Marcos, California, United States

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