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

Study Overview
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Brief Summary
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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.

Detailed Description
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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
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AdV-tk + Valacyclovir Therapy in Combination With Surgery and Chemoradiation for Pancreas Cancer

Conditions
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Pancreatic Adenocarcinoma, Pancreatic Cancer

Intervention / Treatment
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* Biological: AdV-tk
* Drug: Valacyclovir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A resectable<br>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<br>* 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<br>Drug: Valacyclovir<br>* 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.<br>* Other names: Valtrex;|
| Experimental: B locally advanced<br>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<br>* 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<br>Drug: Valacyclovir<br>* 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.<br>* Other names: Valtrex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events |  | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 2 years | 
| Progression free survival |  | 2 years | 
| Tumor response including pathologic response |  | 2 months | 
| Functional Assessment of Cancer Therapy - Pancreas (FACT-Hep) |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy, Gene Therapy, Cytotoxicity, Tumor vaccine, Radiation, Surgery, Chemoradiation