Study of the Safety and Efficacy of TH-302 in Combination With Gemcitabine Compared With Gemcitabine Alone in Previously Untreated Patients With Pancreatic Adenocarcinoma

NCT ID: NCT01144455

Last Updated: 2025-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 214 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2014-12-31

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.

Conditions

Pancreatic Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gemcitabine

Gemcitabine: 1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle

Group Type: ACTIVE_COMPARATOR

Gemzar (Gemcitabine)

Intervention Type: DRUG

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: 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

Group Type: EXPERIMENTAL

Gemzar (Gemcitabine)

Intervention Type: DRUG

1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle.

TH-302

Intervention Type: DRUG

240 mg/m2 of TH-302 will be administered IV over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.

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

Group Type: EXPERIMENTAL

Gemzar (Gemcitabine)

Intervention Type: DRUG

1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle.

TH-302

Intervention Type: DRUG

340 mg/m2 of TH-302 will be administered IV over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.

Interventions

Gemzar (Gemcitabine)

1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Gemcitabine; HAP; hypoxia activated prodrug; HAP; hypoxia activated prodrug

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PRA Health Sciences

INDUSTRY

Sponsor Role: collaborator

ImmunoGenesis

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mitesh Borad, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Shantan Reddy, MD

Role: PRINCIPAL_INVESTIGATOR

Lousiana Health Sciences Center - Shreveport

Locations

Birmingham Hematology and Oncology Associates, LLC

Birmingham, Alabama, United States

Mayo Clinic Arizona

Scottsdale, Arizona, United States

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, United States

University of Arizona

Tucson, Arizona, United States

Saint Edward Mercy Medical Center

Fort Smith, Arkansas, United States

Disney Family Cancer Center

Burbank, California, United States

Scripps Clinical Research Services

La Jolla, California, United States

UCLA Medical Center

Los Angeles, California, United States

Palo Alto Medical Foundation

Mountain View, California, United States

Los Palos Oncology and Hematology

Salinas, California, United States

Sharp Memorial Hospital

San Diego, California, United States

California Pacific Medical Center

San Francisco, California, United States

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Hematology Oncology Associates, PC

Stamford, Connecticut, United States

Florida Cancer Institute - New Hope

New Port Richey, Florida, United States

Ocala Oncology Center

Ocala, Florida, United States

Martin Memorial Cancer Center

Stuart, Florida, United States

Atlanta Cancer Care

Atlanta, Georgia, United States

Loyola University Medical Center

Maywood, Illinois, United States

Carle Cancer Center

Urbana, Illinois, United States

Indiana University Melvin and Bren Simon Cancer

Indianapolis, Indiana, United States

Purchase Cancer Group

Paducah, Kentucky, United States

Medical Oncology

Baton Rouge, Louisiana, United States

Ochsner Cancer Institute

New Orleans, Louisiana, United States

LSU Health Sciences Center - Feist Weiller Cancer Center

Shreveport, Louisiana, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Massachusetts Medical Center

Worcester, Massachusetts, United States

Virgina Piper Cancer Institute

Minneapolis, Minnesota, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Hematology and Oncology Associates at BridgePoint

Tupelo, Mississippi, United States

Missouri Cancer Associates

Columbia, Missouri, United States

Montana Cancer Institute Foundation

Missoula, Montana, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

New York Oncology Hematology, P.C.

Hudson, New York, United States

Cancer Care of Western North Carolina, PA

Asheville, North Carolina, United States

Alamance Oncology Hematolgy Associates

Burlington, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Carolina Oncology Specialists, PA

Hickory, North Carolina, United States

Emerywood Hematology and Oncology

High Point, North Carolina, United States

Signal Point Clinical Research Center

Middletown, Ohio, United States

Kaiser Permanente Northwest Region Oncology Hematology

Portland, Oregon, United States

Northwest Cancer Specialists, P.C.

Portland, Oregon, United States

Greater Philadelphia Cancer and Hematology Specialists, P.C.

Philadelphia, Pennsylvania, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Institute for Translational Oncology Research (ITOR)

Greenville, South Carolina, United States

Vanderbilt University Medical Center, Div. of Medical Oncology

Nashville, Tennessee, United States

Texas Oncology-Beaumont, Mamie McFaddin Ward Cancer Center

Beaumont, Texas, United States

Texas Oncology-Dallas Presbyterian Hospital

Dallas, Texas, United States

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

Texas Oncology- Fort Worth - 12th Avenue

Fort Worth, Texas, United States

Texas Oncology-Seton Williamson

Round Rock, Texas, United States

Texas Oncology-Sherman

Sherman, Texas, United States

Texas Oncology-Wichita Falls Texoma Cancer Center

Wichita Falls, Texas, United States

Fairfax Northern Virginia Hematology Oncology, PC

Fairfax, Virginia, United States

Providence Everett Regional Medical Center, Cancer Research Dept.

Everett, Washington, United States

Columbia Basin Hematology and Oncology0

Kennewick, Washington, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

References

Borad MJ, Reddy SG, Bahary N, Uronis HE, Sigal D, Cohn AL, Schelman WR, Stephenson J Jr, Chiorean EG, Rosen PJ, Ulrich B, Dragovich T, Del Prete SA, Rarick M, Eng C, Kroll S, Ryan DP. Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer. J Clin Oncol. 2015 May 1;33(13):1475-81. doi: 10.1200/JCO.2014.55.7504. Epub 2014 Dec 15.

Reference Type: DERIVED

PMID: 25512461 (View on PubMed)

Related Links

http://www.thresholdpharm.com/

Threshold Pharmaceuticals, Inc

Other Identifiers

TH-CR-404

Identifier Type: -

Identifier Source: org_study_id