A Study to Evaluate the Efficacy and Safety of Simtuzumab Combined With Gemcitabine for Metastatic Pancreatic Adenocarcinoma

A Phase 2 Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GS-6624 Combined With Gemcitabine as First Line Treatment for Metastatic Pancreatic Adenocarcinoma

This study will compare the efficacy of simtuzumab (GS-6624) versus placebo in combination with gemcitabine in adults with pancreatic cancer. The treatment phase of this study will be comprised of 2 sequential parts: an open label treatment phase and a double-blinded treatment phase.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Simtuzumab; Drug: Gemcitabine; Drug: Placebo to match simtuzumab

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Ivanovo, Russian Federation, 153040
    • Regional Oncology Dispensary
  • Kursk, Russian Federation, 305035
    • Kursk Regional Oncologic Dispensary
  • Moscow, Russian Federation, 115478
    • State Institution "Blokhin Cancer Research Centre RAMS"
  • Moscow, Russian Federation, 115478
    • Blokhin Cancer Research Center of Russia, Dept. of clinical pharmacology
  • Moscow, Russian Federation, 125367
    • Non-State Institution of healthcare "Central Clinical Hospital #1 OAO RZD
  • Moscow, Russian Federation, 129128
    • Non-state Healthcare Institution "N.A. Semashko Central Clinical Hospital #2 of JSC "Russian Railway
  • Nizhny Novgorod, Russian Federation, 603081
    • State Budgetary Healthcare Institution "Nizhny Novgorod Regional Oncological Dispensary"
  • Omsk, Russian Federation, 644013
    • Budgetary Healthcare Institution of Omsk Region "Clinical Oncologic Dispensary"
  • Saint Petersburg, Russian Federation, 197758
    • Petrov Research Oncology Institute
  • Bashkortostan
    • Ufa, Bashkortostan, Russian Federation, 450054
      • Republic Clinical Oncology Dispensary of the Ministry of Healthcare of Republic of Bashkortostan
  • Kaluga
    • Obninsk, Kaluga, Russian Federation, 249036
      • Medical Radiological Research Center of Russian Academy of Medical Sciences, Obninsk
  • Primorskiy
    • Arkhangelsk, Primorskiy, Russian Federation, 163045
      • State Institution of Healthcare "Arkhangelsk Regional Clinical Oncology Dispensary"
  • Tatarstan
    • Kazan, Tatarstan, Russian Federation, 420029
      • Republican Clinical Oncologic Dispensary of Ministry of health of Republic Tatarstan
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Birmingham Hematology and Oncology Associates, LLC
    • Mobile, Alabama, United States, 36604
      • University of South Alabama Mitchell Cancer Institute
  • California
    • Alhambra, California, United States
      • Central Hematology Oncology Medical Group, Inc.
    • Bakersfield, California, United States
      • Comprehensive Blood And Cancer Center
    • Fresno, California, United States, 93720
      • California Cancer Associates for Research and Excellence (cCare)
    • Long Beach, California, United States
      • Pacific Shores Medical Group
    • Los Angeles, California, United States
      • UCLA Community Oncology Practice
    • Palo Alto, California, United States
      • Stanford University Medical Center
    • Rancho Cucamonga, California, United States, 91730
      • Wilshire Oncology Medical Group, Inc.
    • San Diego, California, United States, 92123
      • Sharp Health Care
    • San Jose, California, United States, 95116
      • San Jose Medical Group
  • Colorado
    • Grand Junction, Colorado, United States
      • Saint Mary's Regional Cancer Center
  • Connecticut
    • Stamford, Connecticut, United States
      • Hematology Oncology Associates, PC
  • Florida
    • Tampa, Florida, United States, 33607
      • Florida Cancer Specialists
  • Georgia
    • Atlanta, Georgia, United States, 30341
      • Georgia Cancer Specialists, P.C.
  • Illinois
    • Chicago, Illinois, United States
      • Northwestern University
  • Kentucky
    • Crestview Hills, Kentucky, United States, 41017
      • Oncology Hematology Care, Inc.
  • Maryland
    • Annapolis, Maryland, United States
      • Anne Arundel Medical Center, Annapolis Oncology Center
  • Michigan
    • Kalamazoo, Michigan, United States
      • West Michigan Cancer Center
    • Southfield, Michigan, United States, 48075
      • Providence Cancer Center Oncology and Hematology Care Clinic-Eastside Portland
  • Mississippi
    • Tupelo, Mississippi, United States
      • Hematology and Oncology Associates at Bridgepoint
  • Missouri
    • Saint Joseph, Missouri, United States
      • Saint Joseph Oncology, Inc.
    • Saint Louis, Missouri, United States, 63108
      • Washington University School of Medicine
  • Montana
    • Missoula, Montana, United States
      • Montana Cancer Institute Foundation c/o Montana Cancer Specialists
  • Nevada
    • Henderson, Nevada, United States
      • Comprehensive Cancer Centers of Nevada
  • New York
    • New York, New York, United States, 10003
      • Saint Luke's-Roosevelt Hospital Center
    • New York, New York, United States
      • Beth Israel Comprehensive Cancer Center
  • North Carolina
    • Durham, North Carolina, United States
      • Duke University Medical Center, Comprehensive Cancer Center
    • High Point, North Carolina, United States
      • Emerywood Hematology and Oncology
  • Ohio
    • Blue Ash, Ohio, United States, 45242
      • Oncology Hematology Care, Inc.
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17109
      • PinnacleHealth
    • Willow Grove, Pennsylvania, United States, 19090
      • Abington Hematology Oncology Associates, Inc.
  • South Carolina
    • Charleston, South Carolina, United States
      • Charleston Hematology Oncology Associates, PA
    • Columbia, South Carolina, United States
      • South Carolina Oncology Associates
  • Tennessee
    • Knoxville, Tennessee, United States
      • Tennessee Cancer Specialists
    • Nashville, Tennessee, United States, 37206
      • Tennessee Oncology, PLLC
  • Texas
    • Corpus Christi, Texas, United States
      • Coastal Bend Cancer Center
    • Dallas, Texas, United States
      • University Of Texas Southwestern Medical Center At Dallas
    • Fort Sam Houston, Texas, United States, 78234
      • San Antonio Military Medical Center
    • Fort Worth, Texas, United States
      • Center for Cancer and Blood Disorders, PC
    • Lubbock, Texas, United States
      • Joe Arrington Cancer Research and Treatment Center
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists
  • Virginia
    • Fairfax, Virginia, United States
      • Virginia Cancer Specialists, PC
    • Richmond, Virginia, United States
      • Virginia Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Initial diagnosis of metastatic pancreatic cancer must have occurred ≤6 weeks prior to the completion of screening.

• The presence of measurable metastatic pancreatic cancer documented by contrast enhanced CT (or MRI) scan in addition to 1 of the following:

  1. Histological diagnosis of pancreatic adenocarcinoma confirmed by pathologist OR

  2. Pathologist confirmed histological/cytological diagnosis of adenocarcinoma consistent with pancreatic origin in conjunction with either:

     1. The presence of a mass in the pancreas OR
     2. A history of resected pancreatic carcinoma
• Measurable disease per RECIST (ver. 1.1)
• ECOG Performance Status of 0 or 1.
• Adequate hepatic, hematologic and renal functions.

Exclusion Criteria:

• A history or evidence of clinically significant disorder other than metastatic cancer of the pancreas.
• A diagnosis of pancreatic islet neoplasms.
• Subject has undergone major surgery other than diagnosis surgery within 4 weeks of randomization
• Presence of biliary obstruction requiring external drainage
• Brain metastases.
• Unstable cardiovascular function within the last 6 months of screening
• Clinically active liver disease, including active viral hepatitis (HBV or HCV) or cirrhosis
• Known HIV infection.
• Uncontrolled hypertension at Screening
• History or presence of any form of cancer, other than pancreatic cancer, within the 3 years prior to enrollment
• Prior or concurrent anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy) for the treatment of inoperable locally advanced or metastatic pancreatic cancer; prior radiotherapy and chemotherapy given as pre-operative neoadjuvant therapy or radio sensitizers for locally advanced pancreatic cancer are allowed.
• Uncontrolled systemic fungal, bacterial or viral infection
• Participation in an investigational drug or device trial with therapeutic intent within 30 days prior to study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Simtuzumab (open-label); Participants will receive simtuzumab 700 mg plus gemcitabine in cycles of 28 days for up to 3 years.	Drug: Simtuzumab; Simtuzumab administered intravenously every 2 weeks for a total of 2 infusions (Days 1 and 15); Other Names: GS-6624; Drug: Gemcitabine; Gemcitabine 1000 mg/m^2 administered intravenously on Days 1, 8, and 15 of each 28-day cycle; Other Names: Gemzar®
Experimental: Simtuzumab 200 mg (randomized); Participants will receive simtuzumab 200 mg plus gemcitabine in cycles of 28 days for up to 3 years.	Drug: Simtuzumab; Simtuzumab administered intravenously every 2 weeks for a total of 2 infusions (Days 1 and 15); Other Names: GS-6624; Drug: Gemcitabine; Gemcitabine 1000 mg/m^2 administered intravenously on Days 1, 8, and 15 of each 28-day cycle; Other Names: Gemzar®
Experimental: Simtuzumab 700 mg (randomized); Participants will receive simtuzumab 700 mg plus gemcitabine in cycles of 28 days for up to 3 years.	Drug: Simtuzumab; Simtuzumab administered intravenously every 2 weeks for a total of 2 infusions (Days 1 and 15); Other Names: GS-6624; Drug: Gemcitabine; Gemcitabine 1000 mg/m^2 administered intravenously on Days 1, 8, and 15 of each 28-day cycle; Other Names: Gemzar®
Placebo Comparator: Placebo (randomized); Participants will receive placebo to match simtuzumab plus gemcitabine in cycles of 28 days for up to 3 years.	Drug: Gemcitabine; Gemcitabine 1000 mg/m^2 administered intravenously on Days 1, 8, and 15 of each 28-day cycle; Other Names: Gemzar®; Drug: Placebo to match simtuzumab; Placebo to match simtuzumab administered intravenously every 2 weeks for a total of 2 infusions (Days 1 and 15)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression free survival is measured as time from date of randomization to the earliest event time of death regardless of cause or first indication of disease progression.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival is measured as time from date of randomization to death regardless of cause.	Up to 3 years
Objective response	Objective response is assessed by the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 as complete response, partial response, stable disease, or progressive disease.	Up to 3 years

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Benson AB 3rd, Wainberg ZA, Hecht JR, Vyushkov D, Dong H, Bendell J, Kudrik F. A Phase II Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab or Placebo in Combination with Gemcitabine for the First-Line Treatment of Pancreatic Adenocarcinoma. Oncologist. 2017 Mar;22(3):241-e15. doi: 10.1634/theoncologist.2017-0024. Epub 2017 Feb 28.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: November 10, 2011
• First Submitted That Met QC Criteria: November 15, 2011
• First Posted (Estimate): November 16, 2011

Study Record Updates

• Last Update Posted (Estimate): March 10, 2015
• Last Update Submitted That Met QC Criteria: February 19, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: Gemcitabine; Pancreatic Cancer; Oncology; Monoclonal Antibody; Phase II; Phase 2; PC; Gilead; Gilead Sciences; GSI; GS-6624
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Adenocarcinoma; 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; Gemcitabine
• Other Study ID Numbers: GS-US-324-0101