Study of the Safety and Efficacy of TH-302 in Combination With Gemcitabine Compared With Gemcitabine Alone in Previously Untreated Patients With Pancreatic Adenocarcinoma
- Conditions
- Pancreatic Adenocarcinoma
- Interventions
- Registration Number
- NCT01144455
- Lead Sponsor
- ImmunoGenesis
- Brief Summary
The purpose of this study is to determine whether Gemcitabine versus Gemcitabine and TH-302 are effective in the treatment of subjects with first-line metastatic pancreatic adenocarcinoma.
- Detailed Description
A hypoxic microenvironment is a characteristic of many solid tumors including pancreatic cancer. The presence of hypoxia in solid tumors is associated with a more malignant phenotype and resistance to chemotherapy. The hypoxia-activated prodrug, TH-302, is designed to selectively physiologically target the hypoxic microenvironment. There is an absence of therapeutic options for subjects with metastatic pancreatic cancer. Gemcitabine provides clinical benefit as a single agent, but median survival is about 6 months. Combining gemcitabine with TH-302 may enable the targeting of both the normoxic and hypoxic regions of pancreatic cancer.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 214
-
At least 18 years of age
-
Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee
-
Locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma proven either by histology or cytology previously untreated with chemotherapy or systemic therapy other than:
- Radiosensitizing doses of 5-fluorouracil;
- Radiosensitizing doses of gemcitabine if relapse occurred at least 6 months after completion of gemcitabine;
- Neoadjuvant chemotherapy if relapse occurred at least 6 months after surgical resection;
- Adjuvant chemotherapy if relapse occurred at least 6 months after completion of adjuvant chemotherapy.
-
Measurable disease by RECIST 1.1 criteria (at least one target lesion outside of previous radiation fields)
-
Documentation of disease progression since any prior therapy
-
ECOG performance status of 0 or 1
-
Life expectancy of at least 3 months
-
Acceptable liver function:
- Bilirubin less than or equal to 1.5 times upper limit of normal
- AST (SGOT) and ALT (SGPT) less than or equal to 2.5 times upper limit of normal (ULN); if liver metastases are present, then less than or equal to 5 times ULN is allowed
-
Acceptable renal function:
a. Serum creatinine less than or equal to ULN
-
Acceptable hematologic status (without hematologic support):
- ANC greater than or equal to 1500 cells/μL
- Platelet count greater than or equal to 100,000/μL
- Hemoglobin greater than or equal to 9.0 g/dL
-
All women of childbearing potential must have a negative serum pregnancy test and male and female subjects must agree to use effective means of contraception (surgical sterilization or the use or barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose
- New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial infarction within 6 months prior to Day 1, unstable arrhythmia or symptomatic peripheral arterial vascular disease
- Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 3 months)
- Previously treated malignancies, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancer from which the subject has been disease-free for at least 5 years
- Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation <90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause systemic or regional hypoxemia
- Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
- Treatment of pancreatic cancer with radiation therapy or surgery within 4 weeks prior to study entry
- Prior therapy with an hypoxic cytotoxin
- Subjects who participated in an investigational drug or device study within 28 days prior to study entry
- Known active infection with HIV, hepatitis B, or hepatitis
- Subjects who have exhibited allergic reactions to a structural compound, biological agent, or formulation (containing solutol and/or propylene glycol) similar to TH- 302
- Females who are pregnant or breast-feeding
- Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
- Unwillingness or inability to comply with the study protocol for any reason
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 240 mg/m2 TH-302 + Gemcitabine Gemzar (Gemcitabine) TH-302: 240 mg/m2 administered IV over 30 minutes Day 1, 8, and 15 of each 28-day cycle Gemcitabine: 1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle 340 mg/m2 TH-302 + Gemcitabine Gemzar (Gemcitabine) TH-302: 340 mg/m2 of TH-302 be administered IV over 30 minutes on Days 1, 8 and 15 of every 28-day cycle. Gemcitabine: 1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle 340 mg/m2 TH-302 + Gemcitabine TH-302 TH-302: 340 mg/m2 of TH-302 be administered IV over 30 minutes on Days 1, 8 and 15 of every 28-day cycle. Gemcitabine: 1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle 240 mg/m2 TH-302 + Gemcitabine TH-302 TH-302: 240 mg/m2 administered IV over 30 minutes Day 1, 8, and 15 of each 28-day cycle Gemcitabine: 1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle Gemcitabine Gemzar (Gemcitabine) Gemcitabine: 1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (59)
Fairfax Northern Virginia Hematology Oncology, PC
🇺🇸Fairfax, Virginia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Atlanta Cancer Care
🇺🇸Atlanta, Georgia, United States
New York Oncology Hematology, P.C.
🇺🇸Hudson, New York, United States
Emerywood Hematology and Oncology
🇺🇸High Point, North Carolina, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Texas Oncology- Fort Worth - 12th Avenue
🇺🇸Fort Worth, Texas, United States
Texas Oncology-Sherman
🇺🇸Sherman, Texas, United States
Indiana University Melvin and Bren Simon Cancer
🇺🇸Indianapolis, Indiana, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
Disney Family Cancer Center
🇺🇸Burbank, California, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Scripps Clinical Research Services
🇺🇸La Jolla, California, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Purchase Cancer Group
🇺🇸Paducah, Kentucky, United States
Missouri Cancer Associates
🇺🇸Columbia, Missouri, United States
Cancer Care of Western North Carolina, PA
🇺🇸Asheville, North Carolina, United States
Alamance Oncology Hematolgy Associates
🇺🇸Burlington, North Carolina, United States
Carolina Oncology Specialists, PA
🇺🇸Hickory, North Carolina, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Texas Oncology-Beaumont, Mamie McFaddin Ward Cancer Center
🇺🇸Beaumont, Texas, United States
Texas Oncology-Seton Williamson
🇺🇸Round Rock, Texas, United States
Providence Everett Regional Medical Center, Cancer Research Dept.
🇺🇸Everett, Washington, United States
Columbia Basin Hematology and Oncology0
🇺🇸Kennewick, Washington, United States
Texas Oncology-Wichita Falls Texoma Cancer Center
🇺🇸Wichita Falls, Texas, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
Saint Edward Mercy Medical Center
🇺🇸Fort Smith, Arkansas, United States
Los Palos Oncology and Hematology
🇺🇸Salinas, California, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Greater Philadelphia Cancer and Hematology Specialists, P.C.
🇺🇸Philadelphia, Pennsylvania, United States
Signal Point Clinical Research Center
🇺🇸Middletown, Ohio, United States
Texas Oncology-Dallas Presbyterian Hospital
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
Martin Memorial Cancer Center
🇺🇸Stuart, Florida, United States
Arizona Oncology Associates, PC - HOPE
🇺🇸Tucson, Arizona, United States
Mayo Clinic Arizona
🇺🇸Scottsdale, Arizona, United States
Montana Cancer Institute Foundation
🇺🇸Missoula, Montana, United States
Ochsner Cancer Institute
🇺🇸New Orleans, Louisiana, United States
Palo Alto Medical Foundation
🇺🇸Mountain View, California, United States
University of Massachusetts Medical Center
🇺🇸Worcester, Massachusetts, United States
Ocala Oncology Center
🇺🇸Ocala, Florida, United States
Hematology Oncology Associates, PC
🇺🇸Stamford, Connecticut, United States
LSU Health Sciences Center - Feist Weiller Cancer Center
🇺🇸Shreveport, Louisiana, United States
Medical Oncology
🇺🇸Baton Rouge, Louisiana, United States
Florida Cancer Institute - New Hope
🇺🇸New Port Richey, Florida, United States
Institute for Translational Oncology Research (ITOR)
🇺🇸Greenville, South Carolina, United States
Hematology and Oncology Associates at BridgePoint
🇺🇸Tupelo, Mississippi, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Birmingham Hematology and Oncology Associates, LLC
🇺🇸Birmingham, Alabama, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
Virgina Piper Cancer Institute
🇺🇸Minneapolis, Minnesota, United States
Northwest Cancer Specialists, P.C.
🇺🇸Portland, Oregon, United States
Vanderbilt University Medical Center, Div. of Medical Oncology
🇺🇸Nashville, Tennessee, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Kaiser Permanente Northwest Region Oncology Hematology
🇺🇸Portland, Oregon, United States