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

NCT00638612 | Completed Phase 1 DMC

• 1 other identifier: PaTK01
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Pancreatic Adenocarcinoma; Pancreatic Cancer

Keywords

Immunotherapy; Gene Therapy; Cytotoxicity; Tumor vaccine; Radiation; Surgery; Chemoradiation

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment emergent adverse events

  2 months

Secondary Outcomes (4)

• 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

Study Arms (2)

A resectable

EXPERIMENTAL

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; Drug: Valacyclovir

B locally advanced

EXPERIMENTAL

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; Drug: Valacyclovir

Interventions

AdV-tk BIOLOGICAL

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

A resectable; B locally advanced

Valacyclovir DRUG

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.

Also known as: Valtrex

A resectable; B locally advanced

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Candel Therapeutics, Inc.: lead

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Scripps Green Hospital/Scripps Cancer Center

La Jolla, California, 92037, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Related 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 pancreatic adenocarcinoma. Cancer Immunol Immunother. 2015 Jun;64(6):727-36. doi: 10.1007/s00262-015-1679-3. Epub 2015 Mar 21.

  PMID: 25795132 RESULT

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Valacyclovir

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Mark Bloomston, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2008
• First Posted: March 19, 2008
• Study Start: August 1, 2008
• Primary Completion: May 1, 2013
• Study Completion: June 1, 2015
• Last Updated: August 25, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)