AdV-tk Therapy With Surgery and Chemoradiation for Pancreas Cancer

Condition(s) targeted: Pancreatic Adenocarcinoma; Pancreatic Cancer

Intervention: AdV-tk (Biological); Valacyclovir (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: Advantagene, Inc.

Official(s) and/or principal investigator(s):
Mark Bloomston, MD, Principal Investigator, Affiliation: Ohio State University

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.

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

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

Primary outcome: 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.

Secondary outcome:

Overall survival

Progression free survival

Tumor response including pathologic response

Quality of life

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

City of Hope Medical Center, Duarte, California 91010, United States; Recruiting
Vincent Chung, MD, Phone: 626-471-9200
Carol Rose, Phone: 626-359-8111, Ext: 62845, Email: crose@coh.org
Vincent Chung, MD, Principal Investigator

Scripps Green Hospital/Scripps Cancer Center, La Jolla, California 92037, United States; Recruiting
Deandra Holland, RN, BSN, Phone: 858-652-5445, Email: holland.deandra@scrippshealth.org
Christopher Marsh, MD, Principal Investigator

The Ohio State University, Columbus, Ohio 43210, United States; Recruiting
Mark Bloomston, MD, Phone: 866-627-7616, Email: osu@emergingmed.com
Mark Bloomston, MD, Principal Investigator

Starting date: November 2007
Last updated: February 4, 2009