Clinical trial NCT01144455: Study of the Safety and Efficacy of TH-302 in Combination With Gemcitabine Compared With Gemcitabine Alone in Previously Untreated Patients With Pancreatic Adenocarcinoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Adenocarcinoma
Keywords: Locally Advanced Unresectable Pancreatic Adenocarcinoma
Metastatic Pancreatic Adenocarcinoma
Locally Advanced Unresectable or Metastatic Pancreatic Adenocarcinoma
Lead sponsor: ImmunoGenesis
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
First posted: 2010-06-15
Enrollment: 214
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

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