Trial record 1 of 1 for:    TH-CR-404
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Study of the Safety and Efficacy of TH-302 in Combination With Gemcitabine Compared With Gemcitabine Alone in Previously Untreated Patients With Pancreatic Adenocarcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
PRA International
Information provided by:
Threshold Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01144455
First received: June 11, 2010
Last updated: July 16, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Pancreatic Adenocarcinoma
Drug: Gemzar (Gemcitabine)
Drug: TH-302
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Cross-over Phase 2 Study of the Safety and Efficacy of Two Dose Levels of TH-302 in Combination With Gemcitabine Compared With Gemcitabine Alone in Previously Untreated Patients With Locally Advanced Unresectable or Metastatic Pancreatic Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Threshold Pharmaceuticals:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response rate (confirmed and unconfirmed) [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Stable Disease rate [ Designated as safety issue: No ]
  • Overall survival (OS) including 6- and 12-month survival [ Designated as safety issue: No ]
  • Event-free survival [ Designated as safety issue: No ]
  • Serum CA 19-9 response rate [ Designated as safety issue: No ]
  • Change in pain intensity as measured by VAS score [ Designated as safety issue: No ]
  • Change in performance status [ Designated as safety issue: No ]

Estimated Enrollment: 165
Study Start Date: June 2010
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Gemcitabine
Gemcitabine: 1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle
Drug: Gemzar (Gemcitabine)
1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle.
Other Name: Gemcitabine
Experimental: 240 mg/m2 TH-302 + 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

Drug: Gemzar (Gemcitabine)
1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle.
Other Name: Gemcitabine
Drug: TH-302
240 mg/m2 of TH-302 will be administered IV over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.
Other Names:
  • HAP
  • hypoxia activated prodrug
Experimental: 340 mg/m2 TH-302 + 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

Drug: Gemzar (Gemcitabine)
1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle.
Other Name: Gemcitabine
Drug: TH-302
340 mg/m2 of TH-302 will be administered IV over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.
Other Names:
  • HAP
  • hypoxia activated prodrug

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. At least 18 years of age
  2. 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
  3. 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.
  4. Measurable disease by RECIST 1.1 criteria (at least one target lesion outside of previous radiation fields)
  5. Documentation of disease progression since any prior therapy
  6. ECOG performance status of 0 or 1
  7. Life expectancy of at least 3 months
  8. Acceptable liver function:

    1. Bilirubin less than or equal to 1.5 times upper limit of normal
    2. 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
  9. Acceptable renal function:

    a. Serum creatinine less than or equal to ULN

  10. Acceptable hematologic status (without hematologic support):

    1. ANC greater than or equal to 1500 cells/μL
    2. Platelet count greater than or equal to 100,000/μL
    3. Hemoglobin greater than or equal to 9.0 g/dL
  11. 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

Exclusion Criteria:

  1. 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
  2. Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 3 months)
  3. 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
  4. 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
  5. Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
  6. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
  7. Treatment of pancreatic cancer with radiation therapy or surgery within 4 weeks prior to study entry
  8. Prior therapy with an hypoxic cytotoxin
  9. Subjects who participated in an investigational drug or device study within 28 days prior to study entry
  10. Known active infection with HIV, hepatitis B, or hepatitis
  11. Subjects who have exhibited allergic reactions to a structural compound, biological agent, or formulation (containing solutol and/or propylene glycol) similar to TH- 302
  12. Females who are pregnant or breast-feeding
  13. 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
  14. Unwillingness or inability to comply with the study protocol for any reason
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01144455

  Hide Study Locations
Locations
United States, Alabama
Birmingham Hematology and Oncology Associates, LLC
Birmingham, Alabama, United States, 35223
United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
University of Arizona
Tucson, Arizona, United States, 85724
Arizona Oncology Associates, PC - HOPE
Tucson, Arizona, United States, 85704
United States, Arkansas
Saint Edward Mercy Medical Center
Fort Smith, Arkansas, United States, 72917
United States, California
Disney Family Cancer Center
Burbank, California, United States, 91505
Scripps Clinical Research Services
La Jolla, California, United States, 92037
UCLA Medical Center
Los Angeles, California, United States, 90095
Palo Alto Medical Foundation
Mountain View, California, United States, 94040
Los Palos Oncology and Hematology
Salinas, California, United States, 93901
Sharp Memorial Hospital
San Diego, California, United States, 92123
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, Colorado
Rocky Mountain Cancer Centers
Denver, Colorado, United States, 80218
United States, Connecticut
Hematology Oncology Associates, PC
Stamford, Connecticut, United States, 06902
United States, Florida
Florida Cancer Institute - New Hope
New Port Richey, Florida, United States, 34655
Ocala Oncology Center
Ocala, Florida, United States, 34471
Martin Memorial Cancer Center
Stuart, Florida, United States, 34994
United States, Georgia
Atlanta Cancer Care
Atlanta, Georgia, United States, 30342
United States, Illinois
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Carle Cancer Center
Urbana, Illinois, United States, 61901
United States, Indiana
Indiana University Melvin and Bren Simon Cancer
Indianapolis, Indiana, United States, 46202
United States, Kentucky
Purchase Cancer Group
Paducah, Kentucky, United States, 42002
United States, Louisiana
Medical Oncology
Baton Rouge, Louisiana, United States, 70809
Ochsner Cancer Institute
New Orleans, Louisiana, United States, 70121
LSU Health Sciences Center - Feist Weiller Cancer Center
Shreveport, Louisiana, United States, 71130
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
University of Massachusetts Medical Center
Worcester, Massachusetts, United States, 01655
United States, Minnesota
Virgina Piper Cancer Institute
Minneapolis, Minnesota, United States, 55407
Mayo Clinic Rochester
Rochester, Minnesota, United States, 55905
United States, Mississippi
Hematology and Oncology Associates at BridgePoint
Tupelo, Mississippi, United States, 38801
United States, Missouri
Missouri Cancer Associates
Columbia, Missouri, United States, 65201
United States, Montana
Montana Cancer Institute Foundation
Missoula, Montana, United States, 59802
United States, Nevada
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89169
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
New York Oncology Hematology, P.C.
Hudson, New York, United States, 12534
United States, North Carolina
Cancer Care of Western North Carolina, PA
Asherville, North Carolina, United States, 28801
Alamance Oncology Hematolgy Associates
Burlington, North Carolina, United States, 27599
Duke University Medical Center
Durham, North Carolina, United States, 27710
Carolina Oncology Specialists, PA
Hickory, North Carolina, United States, 28602
Emerywood Hematology and Oncology
High Point, North Carolina, United States, 27262
United States, Ohio
Signal Point Clinical Research Center
Middletown, Ohio, United States, 45042
United States, Oregon
Kaiser Permanente Northwest Region Oncology Hematology
Portland, Oregon, United States, 97227
Northwest Cancer Specialists, P.C.
Portland, Oregon, United States, 97227
United States, Pennsylvania
Greater Philadelphia Cancer and Hematology Specialists, P.C.
Philadelphia, Pennsylvania, United States, 19114
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15232
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15212
United States, South Carolina
Institute for Translational Oncology Research (ITOR)
Greenville, South Carolina, United States, 29605
United States, Tennessee
Vanderbilt University Medical Center, Div. of Medical Oncology
Nashville, Tennessee, United States, 37232
United States, Texas
Texas Oncology-Beaumont, Mamie McFaddin Ward Cancer Center
Beaumont, Texas, United States, 77702
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390
Texas Oncology-Dallas Presbyterian Hospital
Dallas, Texas, United States, 75231
Texas Oncology- Fort Worth - 12th Avenue
Fort Worth, Texas, United States, 76104
Texas Oncology-Seton Williamson
Round Rock, Texas, United States, 78665
Texas Oncology-Sherman
Sherman, Texas, United States, 75090
Texas Oncology-Wichita Falls Texoma Cancer Center
Wichita Fall, Texas, United States, 76310
United States, Virginia
Fairfax Northern Virginia Hematology Oncology, PC
Fairfax, Virginia, United States, 22031
United States, Washington
Providence Everett Regional Medical Center, Cancer Research Dept.
Everett, Washington, United States, 98201
Columbia Basin Hematology and Oncology0
Kennewick, Washington, United States, 99336
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Threshold Pharmaceuticals
PRA International
Investigators
Principal Investigator: Mitesh Borad, MD Mayo Clinic
Principal Investigator: Shantan Reddy, MD Lousiana Health Sciences Center - Shreveport
  More Information

Additional Information:
No publications provided

Responsible Party: Threshold Pharmaceuticals, Inc (Clinical Manager - Clarence Eng), Threshold Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01144455     History of Changes
Other Study ID Numbers: TH-CR-404
Study First Received: June 11, 2010
Last Updated: July 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Threshold Pharmaceuticals:
Locally Advanced Unresectable Pancreatic Adenocarcinoma
Metastatic Pancreatic Adenocarcinoma
Locally Advanced Unresectable or Metastatic Pancreatic Adenocarcinoma

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on July 22, 2014