Neoadjuvant GMCI Plus Chemoradiation for Advanced Non-Metastatic Pancreatic Adenocarcinoma (PaTK02)

• ClinicalTrials.gov Identifier: NCT02446093
• Recruitment Status: Recruiting
• First Posted: May 18, 2015
• Last Update Posted: December 7, 2020
• Sponsor: Candel Therapeutics, Inc.
• Collaborator: Ohio State University
• Information provided by (Responsible Party): Candel Therapeutics, Inc.

Study Description

Brief Summary:

The purpose of this study is to evaluate Gene Mediated Cytotoxic Immunotherapy (GMCI™) in combination with standard of care chemoradiation and surgery for borderline resectable and unresectable locally advanced pancreatic cancer in patients who have completed induction chemotherapy. GMCI kills tumor cells and creates an immune stimulatory environment in the tumor. Killing tumor cells in an immune stimulatory environment induces the body's immune system to detect and destroy cancer cells. GMCI has shown synergy with radiation and surgery without added toxicity. The hypothesis is that GMCI added to standard of care chemoradiation and surgery after completion of induction chemotherapy will be safe and will improve the clinical outcome for patients with pancreatic cancer.

Condition or disease	Intervention/treatment	Phase
Pancreatic Adenocarcinoma	Biological: GMCI (aglatimagene besadenovec + valacyclovir); Drug: Chemotherapy; Radiation: Radiation; Procedure: Surgery	Phase 2

Detailed Description:

GMCI involves the injection of aglatimagene besadenovec (AdV-tk) into the tumor followed by oral valacyclovir pills to kill tumor cells and stimulate a cancer vaccine effect. The current protocol is designed to deliver multiple courses of GMCI in combination with standard of care chemoradiation and surgery to capitalize on the synergies with the different treatment modalities.

This protocol includes two phases:

• Phase 1b - completed.
• The Phase 2 is a randomized study comparing a test group receiving GMCI added to chemoradiation and surgery to a control arm receiving chemoradiation followed by surgery. Participants will be randomized in a 1:1 ratio to GMCI plus standard of care or standard of care alone. Both arms receive standard of care treatment and evaluations.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Neoadjuvant GMCI Plus Chemoradiation for Advanced Non-Metastatic Pancreatic Adenocarcinoma
• Study Start Date: October 2015
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Test Arm; GMCI + chemoradiation + surgery	Biological: GMCI (aglatimagene besadenovec + valacyclovir); Three courses of GMCI each involving aglatimagene besadenovec injection into the tumor site followed by 14 days of oral valacyclovir.; Other Names: CAN-2409; AdV-tk; Drug: Chemotherapy; Standard of care chemotherapy given with radiation; Radiation: Radiation; Other Name: Standard of care radiation given with chemotherapy; Procedure: Surgery; Pancreaticoduodenectomy (Whipple); Other Name: Pancreatic cancer resection
Active Comparator: Control Arm; Chemoradiation + surgery	Drug: Chemotherapy; Standard of care chemotherapy given with radiation; Radiation: Radiation; Other Name: Standard of care radiation given with chemotherapy; Procedure: Surgery; Pancreaticoduodenectomy (Whipple); Other Name: Pancreatic cancer resection

Outcome Measures

Primary Outcome Measures :

1. Resection rate [ Time Frame: 4 months ]
   The percentage of patients receiving an R0 resection will be compared between the two arms.
2. Safety graded by CTC ver4.0 [ Time Frame: 6 months ]
   Frequency of adverse events will be compared between the two arms

Secondary Outcome Measures :

1. Overall survival [ Time Frame: 2 years ]
   The percentage of patients alive at 2 years will be compared between the two arms.
2. Progression-free survival [ Time Frame: 2 years ]
   The PFS curves will be estimated using the Kaplan-Meier method.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 76 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Pathological diagnosis of pancreatic adenocarcinoma adequately treated with induction chemotherapy for at least 2 months such that they are a candidate for localized therapy with chemoradiation followed by surgery with or without major vascular resection.
• Patients must be deemed to be in adequate health to undergo major surgery (pancreaticoduodenectomy)
• Tumor accessible for injection that is classified as borderline-resectable or locally advanced but considered potentially resectable after central review by surgical investigators (based upon pre-induction chemotherapy imaging). Resection may include major vascular resection with reconstruction as needed.
• Age 18-76 years
• Performance status ECOG 0-1
• SGOT (AST)<3x upper limit of normal
• Total bilirubin ≤2mg/dl
• Creatinine<2mg/dl
• Calculated creatinine clearance >30ml/m
• WBC>3000/mm3
• Absolute neutrophil count (ANC)>1500/mm3
• Platelets>100,000/mm3
• Hemoglobin > 9 g/dL.
• Patients must give study specific informed consent prior to enrollment

Exclusion Criteria:

• Primary hepatic dysfunction including known cirrhosis or active hepatitis. Patients with biliary obstruction must be stented prior to initiating treatment.
• Evidence of clinically significant pancreatitis as determined by the investigator
• Evidence of significant ascites as determined by the investigator
• Patients on systemic corticosteroids (>10 mg prednisone per day or equivalent) or other systemic immunosuppressive drugs
• Known to be HIV+
• Pregnant or breast-feeding. Female patients of childbearing age must have negative serum or urine pregnancy test within 1 week of beginning therapy.
• Other current malignancy (except squamous or basal cell skin cancers)
• Other serious co-morbid illness or compromised organ function
• Known sensitivity or allergic reactions to acyclovir or valacyclovir

Contacts and Locations

Locations

United States, Florida

Lee Health/Regional Cancer Center; Recruiting

Fort Myers, Florida, United States, 33905

Contact: Alina A Ward 239-343-9547 alina.ward@LeeHealth.org

Contact: Mark Bloomston, MD (239) 333-0995 mark.bloomston@21co.com

Principal Investigator: Mark Bloomston, M.D

United States, Ohio

Ohio State University; Recruiting

Columbus, Ohio, United States, 43210

Contact: Shona Taylor 614-685-4337 ext 8230 Shona.Taylor@osumc.edu

Contact: Mary Dillhoff, MD 614-293-4583 Mary.Dillhoff@osumc.edu

Principal Investigator: Mary Dillhoff, MD

United States, Virginia

University of Virginia; Recruiting

Charlottesville, Virginia, United States, 22903

Contact: Sallie Mannen 434-297-5724 sbm8qz@virginia.edu

Principal Investigator: Tri M Le, MD

Mexico

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran; Recruiting

Mexico City, Mexico, 14080

Contact: Luis Uscanga, M.D +52 (55)54870900 ext 4401 luis.uscangad@gmail.com

Sponsors and Collaborators

Candel Therapeutics, Inc.

Ohio State University

More Information

• Responsible Party: Candel Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02446093
• Other Study ID Numbers: PaTK02
• First Posted: May 18, 2015
• Last Update Posted: December 7, 2020
• Last Verified: December 2020

Keywords provided by Candel Therapeutics, Inc.:

pancreas cancer; immunotherapy; GMCI; AdV-tk; aglatimagene besadenovec

Additional relevant MeSH terms:

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Valacyclovir; Antiviral Agents; Anti-Infective Agents