A Study of TNFerade™ Biologic With 5-FU and Radiation Therapy for First-Line Treatment of Unresectable Locally Advanced Pancreatic Cancer

Pancreatic Cancer Clinical Trial

Official title:

A Randomized, Phase II/III, Study of TNFerade™ Biologic With 5-FU and Radiation Therapy for First-line Treatment of Unresectable Locally Advanced Pancreatic Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00051467
• Other study ID #: GV-001.004
• Status: Completed
• Phase: Phase 3
• First received: January 10, 2003
• Last updated: February 22, 2012

Study information

• Verified date: May 2011
• Source: GenVec
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this study is to assess the safety and effectiveness of TNFerade™ Biologic when administered concurrently with 5-FU and radiation therapy as first-line treatment of unresectable locally advanced pancreatic cancer.

TNFerade™ is a replication deficient adenovirus vector containing the gene for TNF-alpha controlled by a chemoradiation inducible promoter. This allows the expression of TNF-alpha to be greatest in the area receiving radiation. TNF-alpha is a cytokine that has been shown to have potent anti-cancer activities but, due to systemic toxicity, could not be delivered at effective doses. TNFerade™ Biologic is a novel way of selective delivery of TNF-alpha to tumor cells.

TNFerade™ Biologic will be injected during five weekly injection sessions, concomitant with radiation and 5-FU. TNFerade™ Biologic will be administered by direct intratumoral injection using a percutaneous approach (PTA) or endoscopic ultrasound (EUS).

Other known NCT identifiers

• NCT00049647

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Age =18 years old

• Patients with unresectable, locally advanced adenocarcinoma of the pancreas proven by biopsy or cytology (defined as direct extension to the SMA and/or celiac axis with absence of a fat plane between the low-density tumor and these arterial structures, or loss of patent superior mesenteric-portal vein confluence), who have not received previous treatment for pancreatic cancer. Patients who have been surgically explored and deemed unresectable on that basis are eligible, provided other entry criteria are met

• Informed consent

• Karnofsky performance status = or >70%

• Life expectancy greater than 3 months

• Measurable disease

Exclusion Criteria

• Metastatic (stage IV) disease (including involvement of the colon, adrenals, or kidney, or radiographic evidence of peritoneal seeding)

• Patients with ascites detected by CT, US or MRI

• Patients with bulky celiac adenopathy (i.e., > 2.5 cm)

• Diagnosis of islet cell tumor of the pancreas, lymphoma of the pancreas

• History of other malignancy in the past 2 years except carcinoma in situ of the cervix or bladder, non-melanomatous skin cancer or localized early stage prostate cancer

• Previous chemotherapy or radiation for pancreatic cancer or previous radiation to the target field

• Liver enzymes >3 x ULN (ALT, AST, total bilirubin, alkaline phosphatase)

• Coagulopathy (INR >1.5, PTT ratio >1.5)

• Renal insufficiency (serum creatinine >2.0 mg/dL)

• Significant anemia (e.g. hematocrit <28% or hemoglobin <9 g/dL) (may have RBC transfusion), or thrombocytopenia (platelet count <100,000/µL); or neutropenia (ANC <1500/µL)

• Patients with clinically significant pancreatitis within 12 weeks of treatment

• Pancreatic pseudocyst

• Contraindication to both percutaneous- and endoscopic- guided delivery

• Patients with history of deep venous thrombosis or pulmonary embolus

• Patients with doppler evidence of deep venous thrombosis at screening

• Patients with history of coagulopathy or known thrombophilic disorders

• Patients receiving hormone replacement therapy including oral contraceptives within 2 weeks prior to Day 1.

• Clinical evidence of active infection of any type, including hepatitis B or C virus

• Pregnant or lactating women. It is recommended that both men and women use condoms or another barrier method of birth control for at least 8 weeks following the last administration of TNFerade™ biologic and some form of birth control for at least 1 year

• Experimental medications within the last 4 weeks prior to Day 1

• Surgery within the last 4 weeks prior to Day 1 (if patient was ambulatory within 48 hours of surgery, patient may be considered eligible)

• Chronic systemic corticosteroid use at superphysiologic doses (greater than 10mg prednisone per day or equivalent)

• Significant concurrent medical or psychiatric illness which, in the opinion of the investigator, would interfere with the patient's ability to participate in the trial

Please note that there are additional entry criteria. The study center will determine if you meet all criteria. If you do qualify to participate, study personnel will explain the study and answer any questions you may have. You can decide whether or not you wish to participate but if you do not qualify for this trial, study staff will explain the reasons. Please contact your local center listed below, or call the toll free PACT study line for assistance at 1-888-344-6096

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Genetic:
• TNFerade

Locations

Country	Name	City	State
United States	Winship Cancer Center, Emory University	Atlanta	Georgia
United States	Johns Hopkins Medical Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	The Universtiy of Chicago Medical Center	Chicago	Illinois
United States	Mary Crowley Medical Center	Dallas	Texas
United States	Univeristy of Texas Southwestern Medical Center	Dallas	Texas
United States	University of Colorado Health Science Center Facility	Denver	Colorado
United States	Wayne State University, Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	Leo W. Jenkins Cancer Center	Greenville	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University Medical Goup	Indianapolis	Indiana
United States	Research Medical Center	Kansas City	Missouri
United States	University of California San Diego Moores Cancer Center	La Jolla	California
United States	UCLA School of Medicine, Division of Hematology-Oncology	Los Angeles	California
United States	University of Wisconsin, Division of Neoplastic Diseases & Related Disorders	Milwaukee	Wisconsin
United States	Beth Israel Medical Center, BI Cancer Center	New York	New York
United States	St. James Hospital and Health Centers Comprehensive Cancer Institute	Olympia Fields	Illinois
United States	UC Irvine Medical Center	Orange	California
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Washington University	St. Louis	Missouri
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	Tampa General Hospital	Tampa	Florida
United States	Georgetown, MedStar Research Institute	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
GenVec

Country where clinical trial is conducted

United States,