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

Pancreatic Cancer Clinical Trial

— PaTK01  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00638612
• Other study ID #: PaTK01
• Status: Completed
• Phase: Phase 1
• Start date: August 2008
• Est. completion date: June 2015

Study information

• Verified date: August 2023
• Source: Candel Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: June 2015
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pancreatic Adenocarcinoma
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	The Ohio State University	Columbus	Ohio
United States	City of Hope Medical Center	Duarte	California
United States	Scripps Green Hospital/Scripps Cancer Center	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
Candel Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Aguilar LK, Shirley LA, Chung VM, Marsh CL, Walker J, Coyle W, Marx H, Bekaii-Saab T, Lesinski GB, Swanson B, Sanchez D, Manzanera AG, Aguilar-Cordova E, Bloomston M. Gene-mediated cytotoxic immunotherapy as adjuvant to surgery or chemoradiation for pancr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment emergent adverse events		2 months
Secondary	Overall survival		2 years
Secondary	Progression free survival		2 years
Secondary	Tumor response including pathologic response		2 months
Secondary	Functional Assessment of Cancer Therapy - Pancreas (FACT-Hep)		2 years