Clinical Trials /

Neoadjuvant GMCI Plus Chemoradiation for Advanced Non-Metastatic Pancreatic Adenocarcinoma

NCT02446093

Description:

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.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant GMCI Plus Chemoradiation for Advanced Non-Metastatic Pancreatic Adenocarcinoma
  • Official Title: Neoadjuvant GMCI Plus Chemoradiation for Advanced Non-Metastatic Pancreatic Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: PaTK02
  • NCT ID: NCT02446093

Conditions

  • Pancreatic Adenocarcinoma

Interventions

DrugSynonymsArms
GMCIAdV-tk (aglatimagene besadenovec) + valacyclovirTest Arm
ChemotherapyTest Arm

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Test ArmExperimentalGMCI + chemoadiation + surgery
  • GMCI
  • Chemotherapy
Control ArmActive ComparatorChemoradiation + surgery
  • Chemotherapy

Eligibility 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
      
Maximum Eligible Age:76 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Resection rate
Time Frame:4 months
Safety Issue:
Description:The percentage of patients receiving an R0 resection will be compared between the two arms.

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Advantagene, Inc.

Trial Keywords

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

Last Updated

June 28, 2019