Official Title: “AdV-tk + Valacyclovir Therapy in Combination With Surgery and Chemoradiation for Pancreas Cancer”

The purpose of this study is to evaluate the safety and potential efficacy of Gene Mediated Cytotoxic Immunotherapy for pancreatic cancer. The approach uses an adenoviral vector (disabled virus) engineered to express the Herpes thymidine kinase gene (AdV-tk), followed by an antiherpetic prodrug, valacyclovir. The AdV-tk vector is injected into the tumor or tumor bed at the time of biopsy or standard tumor surgery after which valacyclovir pills are taken for 14 days. Two courses of AdV-tk, each followed by valacyclovir, are given as adjuvant to standard of care therapies (surgery and/or chemoradiation) which have been shown to work cooperatively with AdV-tk to kill tumor cells. Arm A is for resectable tumors in which the first course is given prior to surgery and the second is at the time of surgery. Arm B is for locally advanced disease in which both AdV-tk injections are administered by needle injection into the tumor before and during chemoradiation. The hypothesis is that this combination therapy can be safely delivered and will lead to improvement in the clinical outcome for patients with pancreatic cancer.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety Study

Study Primary Completion Date: December 2009

Intervention(s) in this Clinical Trial

• Biological: AdV-tk
  • Four dose levels of AdV-tk with a fixed dose level of valacyclovir are evaluated independently in the two arms of the study due to differences in the concomitant standard of care treatments. The first AdV-tk course is given prior to surgery or radiation by CT or EUS guided injection into the tumor followed by 14 days of valacyclovir. The second AdV-tk injection is into the tumor bed at the time of surgery in Arm A or same as the first injection in Arm B again followed by 14 days of valacyclovir. The AdV-tk dose levels are: Level 1= 3x10e10 vector particles (vp), Level 2= 1x10e11 vp, Level 3= 3x10e11 vp, Level 4= 1x10e12 vp
• Drug: Valacyclovir
  • Valacyclovir caplets at a dose of 2 grams orally three times per day is administered for 14 days starting 1-3 days after each of the two AdV-tk injections in both arms.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Arm A is for resectable tumors. The first AdV-tk course is given prior to surgery by CT or EUS guided injection into the tumor followed by 14 days of valacyclovir. The second AdV-tk injection is into the tumor bed at the time of surgery again followed by 14 days of valacyclovir.
• Experimental: B
  • Arm B is for locally advanced tumors for which chemoradiation is the planned standard of care treatment. AdV-tk is delivered by CT or EUS guided injection into the tumor. The first AdV-tk injection is given prior to starting chemoradiation and the second in week 3 of chemoradiation. Both injections are followed by 14 days of valacyclovir.

Primary Measures

• Safety based on symptoms and laboratory abnormalities not expected from standard of care treatments or natural history of the disease process. Toxicity grading uses NCI CTC version 3. Dose limiting toxicity is specifically defined in the protocol.
  • Time Frame: 2 months
    Safety Issue?: Yes

Secondary Measures

• Overall survival
  • Time Frame: 2 years
    Safety Issue?: No
• Progression free survival
  • Time Frame: 2 years
    Safety Issue?: No
• Tumor response including pathologic response
  • Time Frame: 2 months
    Safety Issue?: No
• Quality of life
  • Time Frame: 2 years
    Safety Issue?: No

Inclusion Criteria:

• Must have presumed pancreatic adenocarcinoma based on clinical and radiologic evaluation with identifiable tumor accessible for injection (pathologic diagnosis of pancreatic adenocarcinoma must be made prior to AdV-tk injection
• No evidence of metastases
• For Arm A, resectable disease. For Arm B, locally advanced disease.
• Performance status must be ECOG 0-2
• SGOT (AST)<3x upper limit of normal
• Serum creatinine<2mg/dl and calculated creatinine clearance >10ml/min
• Platelets>100,000/mm3 and WBC>3000/mm3 and ANC>1500/mm3
• Must give study specific informed consent prior to enrollment

Exclusion Criteria:

• Prior or ongoing liver disease including known cirrhosis, hepatitis B or C infection but not to exclude patients with a distant history of resolved hepatitis A infection
• Clinical pancreatitis in past 3 months
• Patients on corticosteroids or other immunosuppressive drugs
• Known HIV+ patients
• Patients with acute infections (viral, bacterial or fungal infections requiring therapy)
• Pregnant or breast-feeding patients. Female patients of childbearing age must have negative serum or urine pregnancy test within 1 week of beginning therapy
• Evidence of distant metastatic disease or other malignancy (except squamous or basal cell skin cancers) and no prior abdominal radiation therapy or prior treatment for pancreatic cancer
• Other serious co-morbid illness or compromised organ function

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Advantagene, Inc.

Overall Clinical Trial Officials and Contacts

Mark Bloomston, MD Principal Investigator Ohio State University  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00638612

Study ID Number: PaTK01

ClinicalTrials.gov Identifier: NCT00638612

Health Authority: United States: Food and Drug Administration