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).
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
University of South Alabama, Mitchell Cancer Institute, Mobile, Alabama, United States; Recruiting
Pamela Francisco, Phone: 251-665-8019, Email: pfrancisco@usouthal.edu
Scottsdale Clinical Research Institute, Scottsdale, Arizona, United States; Recruiting
Patricia Hopper, RN, Phone: 480-323-1350, Email: phopper@shc.org
University of Arizona, Tucson, Arizona, United States; Recruiting
Yrma Obregon, Phone: 520-694-9081, Email: yobregon@azccl.arizona.edu
UCLA School of Medicine, Division of Hematology-Oncology, Los Angeles, California, United States; Recruiting
Myung Lee, RN, Phone: 310-825-4494, Email: mylee@mednet.ucla.edu
UC Irvine Medical Center, Orange, California, United States; Recruiting
Sentelle Eubanks, Phone: 714-456-3860, Email: sentelle@uci.edu
San Francisco General Hospital, San Francisco, California, United States; Recruiting
Lipo Chang, Phone: 415-206-3044, Email: lchang@sfghsurg.ucsf.edu
University of California San Diego Moores Cancer Center, La Jolla, California, United States; Recruiting
Jonathan Sohn, Phone: 858-822-6039, Email: jsohn@ucsd.edu
Glensdale Adventist Medical Center, Glendale, California, United States; Recruiting
Maria Brown, MPH, Phone: 818-409-6687, Email: brownmt@ah.org
University of Colorado Health Science Center Facility, Denver, Colorado, United States; Recruiting
Somer Aly, Phone: 303-724-1877, Email: Somer.Aly@uchsc.edu
Georgetown, MedStar Research Institute, Washington, District of Columbia, United States; Recruiting
Lisa Ley, Phone: 202-687-6653, Email: leyl@georgetown.edu
Tampa General Hospital, Tampa, Florida, United States; Recruiting
Jennifer Cooper, Phone: 813-844-4218, Email: jcooper@hsc.usf.edu
Winship Cancer Center, Emory University, Atlanta, Georgia, United States; Recruiting
Shequila Harper, B.S., CRC, Phone: 404-778-4449, Email: Shequila.harper@emoryhealthcare.org
The Universtiy of Chicago Medical Center, Chicago, Illinois, United States; Recruiting
Rose L Arrieta, RN, Phone: 773-834-7964, Email: rarrieta@surgery.bsd.uchicago.edu
St. James Hospital and Health Centers Comprehensive Cancer Institute, Olympia Fields, Illinois, United States; Recruiting
Lourdes Richardson, Phone: 708-679-2217, Email: lourdes.richardson@ssfhs.org
University of Kentucky Medical Center, Lexington, Kentucky, United States; Recruiting
Rebecca Shelton, Email: rshel1@email.uky.edu
Johns Hopkins Medical Center, Baltimore, Maryland, United States; Recruiting
Yasmin Khan, Phone: 410-502-0830, Email: ykhan1@jhmi.edu
The Neely Center for Clinical Cancer Research, Tufts New England Medical Center, Dept of Hematology and Oncology, Boston, Massachusetts, United States; Recruiting
Stephen J. Cropper, Phone: 617-636-8885, Email: scropper@tufts-nemc.org
Washington University, St. Louis, Missouri, United States; Recruiting
Leslie Foster, Phone: 314-362-8547, Email: fosterl@ccadmin.wustl.edu
Billings Clinic, Billings, Montana, United States; Recruiting
Kathy Wilkinson, Phone: 406-238-2866, Email: Kwilkinson@billingsclinic.org
Beth Israel Medical Center, BI Cancer Center, New York, New York, United States; Recruiting
Sherly Jacob-Perez, Phone: 212-844-8292, Email: sjacob@chpnet.org
Cleveland Clinic Foundation, Cleveland, Ohio, United States; Recruiting
Shelley Robinson, Phone: 216-444-9668, Email: robinss@ccf.org
Legacy Clinical Research, Portland, Oregon, United States; Recruiting
Lorraine Donison, Phone: 503-413-7945, Email: ldonison@lhs.org
Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, United States; Recruiting
Alexis Haynes, Phone: 215-615-4142, Email: alexis.hayes@uphs.upenn.edu
Cancer Centers of the Carolinas, Greenville, South Carolina, United States; Recruiting
Julie Martin, APRN, NP, Phone: 864-679-3966, Email: julie.martin@usoncology.com
Charleston Cancer Center, Charleston, South Carolina, United States; Recruiting
Debi Craft, BS, RN, CCRC, Phone: 843-576-1006, Email: debi.craft@charlestonCancer.com
Mary Crowley Medical Center, Dallas, Texas, United States; Recruiting
Paige(Aimee) Davis, Phone: 214-370-1855, Email: adavis@mcmrc.com
Baylor College of Medicine, Houston, Texas, United States; Recruiting
Glenn Wilson, Phone: 713-798-3468, Email: ggwilson@bcm.tmc.edu
Virginia Commonwealth University, Richmond, Virginia, United States; Recruiting
Diane Holdford, RN, BSN, CCRC, Phone: 804-828-0296, Email: djholdfo@hsc.vcu.edu
Virginia Mason Medical Center, Seattle, Washington, United States; Recruiting
Nicoline Lomah, MS, CCRC, Phone: 206-341-0501, Email: gasnbl@vmmc.org
Marshfield Clinic Research Foundation, Marshfield, Wisconsin, United States; Recruiting
Wendy Foth, Phone: 715-389-7549, Email: foth.wendy@mcrf.mfldclin.edu
University of Wisconsin, Division of Neoplastic Diseases & Related Disorders, Milwaukee, Wisconsin, United States; Recruiting
Brenda Davies, Phone: 414-805-4639, Email: bdavies@mcw.edu
