AdV-tk Therapy With Surgery and Chemoradiation for Pancreas Cancer (PaTK01) - Full Text View

Sponsor:	Advantagene, Inc.
Information provided by (Responsible Party):	Advantagene, Inc.
ClinicalTrials.gov Identifier:	NCT00638612

Purpose

The purpose of this Phase 1 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.

Condition	Intervention	Phase
Pancreatic Adenocarcinoma Pancreatic Cancer	Biological: AdV-tk Drug: Valacyclovir	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	AdV-tk + Valacyclovir Therapy in Combination With Surgery and Chemoradiation for Pancreas Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Pancrelipase Valaciclovir Valacyclovir hydrochloride Ultrase

U.S. FDA Resources

Further study details as provided by Advantagene, Inc.:

Primary Outcome 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Progression free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Tumor response including pathologic response [ Time Frame: 2 months ] [ Designated as safety issue: No ]
Quality of life [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Resectability [ Time Frame: 2 years ] [ Designated as safety issue: No ]
CA 19-9 response [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	November 2007
Estimated Primary Completion Date:	May 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	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. Other Name: Valtrex
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. Enrollment has been completed for Arm B.	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. Other Name: Valtrex

Arms

Assigned Interventions

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.

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.

Other Name: Valtrex

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.

Enrollment has been completed for Arm B.

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.

Other Name: Valtrex

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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
For Arm A, resectable disease. Arm B for locally advanced disease has completed accrual.
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:

Primary hepatic dysfunction including active hepatitis but not to exclude patients due to obstructive jaundice. If obstructive jaundice is clinically significant, bilirubin should be stable or decreasing prior to enrollment.
Evidence of clinically significant pancreatitis as determined by the investigator.
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 at the time of enrollment 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00638612

Locations

United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Scripps Green Hospital/Scripps Cancer Center
La Jolla, California, United States, 92037
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210

Sponsors and Collaborators

Advantagene, Inc.

Investigators

Principal Investigator:

Mark Bloomston, MD

Ohio State University

More Information

No publications provided

Responsible Party:	Advantagene, Inc.
ClinicalTrials.gov Identifier:	NCT00638612 History of Changes
Other Study ID Numbers:	PaTK01, 1R43CA119847
Study First Received:	March 6, 2008
Last Updated:	September 12, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Advantagene, Inc.:

Immunotherapy
Gene Therapy
Cytotoxicity
Tumor vaccine

Radiation
Surgery
Chemoradiation

Additional relevant MeSH terms:

Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases

Pancreatic Diseases
Endocrine System Diseases
Pancrelipase
Valacyclovir
Acyclovir
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on February 09, 2012