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

NCT01144455 | Completed Phase 2 Results DMC

• 1 other identifier: TH-CR-404
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 59

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.

Conditions

Pancreatic Adenocarcinoma

Keywords

Locally Advanced Unresectable Pancreatic Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Locally Advanced Unresectable or Metastatic Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  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

  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

Study Arms (3)

Gemcitabine

ACTIVE COMPARATOR

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

Drug: Gemzar (Gemcitabine)

240 mg/m2 TH-302 + Gemcitabine

EXPERIMENTAL

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); Drug: TH-302

340 mg/m2 TH-302 + Gemcitabine

EXPERIMENTAL

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); Drug: TH-302

Interventions

Gemzar (Gemcitabine) DRUG

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

Also known as: Gemcitabine

240 mg/m2 TH-302 + Gemcitabine; 340 mg/m2 TH-302 + Gemcitabine; Gemcitabine

TH-302 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.

Also known as: HAP, hypoxia activated prodrug

240 mg/m2 TH-302 + Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• ImmunoGenesis: lead
• PRA Health Sciences: collaborator

Study Sites (59)

Birmingham Hematology and Oncology Associates, LLC

Birmingham, Alabama, 35223, United States

Location

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, 85704, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

Saint Edward Mercy Medical Center

Fort Smith, Arkansas, 72917, United States

Location

Disney Family Cancer Center

Burbank, California, 91505, United States

Location

Scripps Clinical Research Services

La Jolla, California, 92037, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Palo Alto Medical Foundation

Mountain View, California, 94040, United States

Location

Los Palos Oncology and Hematology

Salinas, California, 93901, United States

Location

Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Hematology Oncology Associates, PC

Stamford, Connecticut, 06902, United States

Location

Florida Cancer Institute - New Hope

New Port Richey, Florida, 34655, United States

Location

Ocala Oncology Center

Ocala, Florida, 34471, United States

Location

Martin Memorial Cancer Center

Stuart, Florida, 34994, United States

Location

Atlanta Cancer Care

Atlanta, Georgia, 30342, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Carle Cancer Center

Urbana, Illinois, 61901, United States

Location

Indiana University Melvin and Bren Simon Cancer

Indianapolis, Indiana, 46202, United States

Location

Purchase Cancer Group

Paducah, Kentucky, 42002, United States

Location

Medical Oncology

Baton Rouge, Louisiana, 70809, United States

Location

Ochsner Cancer Institute

New Orleans, Louisiana, 70121, United States

Location

LSU Health Sciences Center - Feist Weiller Cancer Center

Shreveport, Louisiana, 71130, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Massachusetts Medical Center

Worcester, Massachusetts, 01655, United States

Location

Virgina Piper Cancer Institute

Minneapolis, Minnesota, 55407, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Hematology and Oncology Associates at BridgePoint

Tupelo, Mississippi, 38801, United States

Location

Missouri Cancer Associates

Columbia, Missouri, 65201, United States

Location

Montana Cancer Institute Foundation

Missoula, Montana, 59802, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

New York Oncology Hematology, P.C.

Hudson, New York, 12534, United States

Location

Cancer Care of Western North Carolina, PA

Asheville, North Carolina, 28801, United States

Location

Alamance Oncology Hematolgy Associates

Burlington, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Carolina Oncology Specialists, PA

Hickory, North Carolina, 28602, United States

Location

Emerywood Hematology and Oncology

High Point, North Carolina, 27262, United States

Location

Signal Point Clinical Research Center

Middletown, Ohio, 45042, United States

Location

Kaiser Permanente Northwest Region Oncology Hematology

Portland, Oregon, 97227, United States

Location

Northwest Cancer Specialists, P.C.

Portland, Oregon, 97227, United States

Location

Greater Philadelphia Cancer and Hematology Specialists, P.C.

Philadelphia, Pennsylvania, 19114, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Institute for Translational Oncology Research (ITOR)

Greenville, South Carolina, 29605, United States

Location

Vanderbilt University Medical Center, Div. of Medical Oncology

Nashville, Tennessee, 37232, United States

Location

Texas Oncology-Beaumont, Mamie McFaddin Ward Cancer Center

Beaumont, Texas, 77702, United States

Location

Texas Oncology-Dallas Presbyterian Hospital

Dallas, Texas, 75231, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390, United States

Location

Texas Oncology- Fort Worth - 12th Avenue

Fort Worth, Texas, 76104, United States

Location

Texas Oncology-Seton Williamson

Round Rock, Texas, 78665, United States

Location

Texas Oncology-Sherman

Sherman, Texas, 75090, United States

Location

Texas Oncology-Wichita Falls Texoma Cancer Center

Wichita Falls, Texas, 76310, United States

Location

Fairfax Northern Virginia Hematology Oncology, PC

Fairfax, Virginia, 22031, United States

Location

Providence Everett Regional Medical Center, Cancer Research Dept.

Everett, Washington, 98201, United States

Location

Columbia Basin Hematology and Oncology0

Kennewick, Washington, 99336, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• 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.

  PMID: 25512461 DERIVED

Related Links

• Threshold Pharmaceuticals, Inc

MeSH Terms

Interventions

Gemcitabine; TH 302

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Thomas Wilson
• Organization: Threshold Pharmaceuticals

twilson@thresholdpharm.com

302-359-0565

Study Officials

• Mitesh Borad, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Shantan Reddy, MD

  Lousiana Health Sciences Center - Shreveport

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2010
• First Posted: June 15, 2010
• Study Start: June 1, 2010
• Primary Completion: September 1, 2013
• Study Completion: December 1, 2014
• Last Updated: May 11, 2025
• Results First Posted: October 25, 2017

Record last verified: 2025-05

Locations

US (59)