Clinical trial NCT00051467: A Study of TNFerade™ Biologic With 5-FU and Radiation Therapy for First-Line Treatment of Unresectable Locally Advanced Pancreatic Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pancreatic Cancer
Lead sponsor: GenVec
Sponsor class: INDUSTRY
First posted: 2003-01-13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA School of Medicine, Division of Hematology-Oncology
state: California
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: Denver
country: United States
facility: University of Colorado Health Science Center Facility
state: Colorado
city: Washington
country: United States
facility: Georgetown, MedStar Research Institute
state: District of Columbia
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Center, Emory University
state: Georgia
city: Chicago
country: United States
facility: The Universtiy of Chicago Medical Center
state: Illinois
city: Olympia Fields
country: United States
facility: St. James Hospital and Health Centers Comprehensive Cancer Institute
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Medical Goup
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins Medical Center
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University, Karmanos Cancer Institute
state: Michigan
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Beth Israel Medical Center, BI Cancer Center
state: New York
city: Greenville
country: United States
facility: Leo W. Jenkins Cancer Center
state: North Carolina
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Dallas
country: United States
facility: Mary Crowley Medical Center
state: Texas
city: Dallas
country: United States
facility: Univeristy of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Milwaukee
country: United States
facility: University of Wisconsin, Division of Neoplastic Diseases & Related Disorders
state: Wisconsin
Study officials:
References:
citation: Herman JM, Wild AT, Wang H, Tran PT, Chang KJ, Taylor GE, Donehower RC, Pawlik TM, Ziegler MA, Cai H, Savage DT, Canto MI, Klapman J, Reid T, Shah RJ, Hoffe SE, Rosemurgy A, Wolfgang CL, Laheru DA. Randomized phase III multi-institutional study of TNFerade biologic with fluorouracil and radiotherapy for locally advanced pancreatic cancer: final results. J Clin Oncol. 2013 Mar 1;31(7):886-94. doi: 10.1200/JCO.2012.44.7516. Epub 2013 Jan 22.