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

Pancreatic Adenocarcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01144455
• Other study ID #: TH-CR-404
• Status: Completed
• Phase: Phase 2
• First received: June 11, 2010
• Last updated: November 20, 2017
• Start date: June 2010
• Est. completion date: December 2014

Study information

• Verified date: November 2017
• Source: Threshold Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 214
• Est. completion date: December 2014
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Adenocarcinoma

Intervention

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

Locations

Country	Name	City	State
United States	Cancer Care of Western North Carolina, PA	Asheville	North Carolina
United States	Atlanta Cancer Care	Atlanta	Georgia
United States	Medical Oncology	Baton Rouge	Louisiana
United States	Texas Oncology-Beaumont, Mamie McFaddin Ward Cancer Center	Beaumont	Texas
United States	Birmingham Hematology and Oncology Associates, LLC	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Disney Family Cancer Center	Burbank	California
United States	Alamance Oncology Hematolgy Associates	Burlington	North Carolina
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Texas Oncology-Dallas Presbyterian Hospital	Dallas	Texas
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Providence Everett Regional Medical Center, Cancer Research Dept.	Everett	Washington
United States	Fairfax Northern Virginia Hematology Oncology, PC	Fairfax	Virginia
United States	Saint Edward Mercy Medical Center	Fort Smith	Arkansas
United States	Texas Oncology- Fort Worth - 12th Avenue	Fort Worth	Texas
United States	Institute for Translational Oncology Research (ITOR)	Greenville	South Carolina
United States	Carolina Oncology Specialists, PA	Hickory	North Carolina
United States	Emerywood Hematology and Oncology	High Point	North Carolina
United States	New York Oncology Hematology, P.C.	Hudson	New York
United States	Indiana University Melvin and Bren Simon Cancer	Indianapolis	Indiana
United States	Columbia Basin Hematology and Oncology0	Kennewick	Washington
United States	Scripps Clinical Research Services	La Jolla	California
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	UCLA Medical Center	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Loyola University Medical Center	Maywood	Illinois
United States	Signal Point Clinical Research Center	Middletown	Ohio
United States	Virgina Piper Cancer Institute	Minneapolis	Minnesota
United States	Montana Cancer Institute Foundation	Missoula	Montana
United States	Palo Alto Medical Foundation	Mountain View	California
United States	Vanderbilt University Medical Center, Div. of Medical Oncology	Nashville	Tennessee
United States	Ochsner Cancer Institute	New Orleans	Louisiana
United States	Florida Cancer Institute - New Hope	New Port Richey	Florida
United States	Ocala Oncology Center	Ocala	Florida
United States	Purchase Cancer Group	Paducah	Kentucky
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	Kaiser Permanente Northwest Region Oncology Hematology	Portland	Oregon
United States	Northwest Cancer Specialists, P.C.	Portland	Oregon
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Texas Oncology-Seton Williamson	Round Rock	Texas
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	Mayo Clinic Arizona	Scottsdale	Arizona
United States	Texas Oncology-Sherman	Sherman	Texas
United States	LSU Health Sciences Center - Feist Weiller Cancer Center	Shreveport	Louisiana
United States	Hematology Oncology Associates, PC	Stamford	Connecticut
United States	Martin Memorial Cancer Center	Stuart	Florida
United States	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona
United States	University of Arizona	Tucson	Arizona
United States	Hematology and Oncology Associates at BridgePoint	Tupelo	Mississippi
United States	Carle Cancer Center	Urbana	Illinois
United States	Texas Oncology-Wichita Falls Texoma Cancer Center	Wichita Falls	Texas
United States	University of Massachusetts Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Threshold Pharmaceuticals	PRA Health Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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

External Links

•   Threshold Pharmaceuticals, Inc