Clinical Trials /

Phase 1 Trial of Interleukin 12 Gene Therapy for Metastatic Pancreatic Cancer

NCT03281382

Description:

This phase 1 trial will investigate the toxicity of combining interleukin 12 gene therapy with standard chemotherapy in metastatic pancreatic cancer.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1 Trial of Interleukin 12 Gene Therapy for Metastatic Pancreatic Cancer
  • Official Title: PHASE 1 TRIAL OF ONCOLYTIC ADENOVIRUS-MEDIATED CYTOTOXIC AND IL-12 GENE THERAPY IN COMBINATION WITH CHEMOTHERAPY FOR THE TREATMENT OF METASTATIC PANCREATIC CANCER

Clinical Trial IDs

  • ORG STUDY ID: 11260
  • NCT ID: NCT03281382

Conditions

  • Metastatic Pancreatic Cancer

Interventions

DrugSynonymsArms
Ad5-yCD/mutTKSR39rep-hIL12Investigational Arm

Purpose

This phase 1 trial will investigate the toxicity of combining interleukin 12 gene therapy with standard chemotherapy in metastatic pancreatic cancer.

Detailed Description

      This protocol proposes a phase 1 trial combining oncolytic adenovirus-mediated cytotoxic and
      IL-12 gene therapy with chemotherapy in metastatic pancreatic cancer. Nine subjects (3
      cohorts, 3 subjects/cohort) with metastatic pancreatic cancer will receive a single
      intratumoral injection of the oncolytic Ad5-yCD/mutTKSR39rep-hIL12 adenovirus at one of three
      dose levels (cohort 1- 1 x 1011 vp, cohort 2- 3 x 1011 vp, cohort 3- 1 x 1012 vp). Depending
      on the location of the target lesion, the adenovirus will be injected either through the
      stomach or duodenal wall using endoscopic ultrasound (EUS) guidance. Two days later, subjects
      will be administered (orally) 7 days of 5-fluorocytosine (5-FC) prodrug therapy. Fourteen
      days after completion of the 5-FC prodrug therapy course, subjects will be administered
      chemotherapy at the discretion of the treating physician. On an optional basis, subjects will
      be administered [18F]-FHBG, a HSV-1 TK substrate, and will undergo PET imaging to quantify
      the intensity, persistence, and biodistribution of HSV-1 TK gene expression in the pancreas.

      The primary endpoint is toxicity at day 21. A secondary endpoint is rates of ≥ grade 3 CTCAE
      adverse events. Exploratory endpoints include 1) intensity, persistence, and biodistribution
      of HSV-1 TK gene expression, and 2) association of immunological measurements (i.e., cytokine
      levels, NK cytolytic activity) with toxicity and clinical outcome.
    

Trial Arms

NameTypeDescriptionInterventions
Investigational ArmExperimentalPatients will receive a single intratumoral injection of the oncolytic Ad5-yCD/mutTKSR39rep-hIL12 adenovirus at one of three dose levels. Two days later, subjects will be administered (orally) 7 days of 5-fluorocytosine (5-FC) prodrug therapy. Fourteen days after completion of the 5-FC prodrug therapy course, subjects will be administered chemotherapy at the discretion of the treating physician. On an optional basis, subjects will be administered [18F]-FHBG, a HSV-1 TK substrate, and will undergo PET imaging to quantify the intensity, persistence, and biodistribution of HSV-1 TK gene expression in the pancreas.
  • Ad5-yCD/mutTKSR39rep-hIL12

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically proven (biopsy or cytology) metastatic pancreatic adenocarcinoma.

          -  Age ≥ 18 years.

          -  No prior treatment (surgery, chemotherapy, radiotherapy, or biological therapy) for
             the study cancer.

          -  Zubrod performance score of 0 - 2 within 30 days of registration.

          -  Subjects must have adequate baseline organ function, as assessed by the following
             laboratory values, within 30 days before initiating the study therapy:

               -  Adequate renal function with serum creatinine ≤ 1.8 mg/dL or creatinine clearance
                  ≥ 50 mL/min/m2.

               -  Absolute neutrophil count > 1,000/μL.

               -  Hemoglobin > 8.0 g/dL.

               -  Platelet count > 100,000/μL.

               -  Bilirubin < 2.0 mg/dL.

               -  SGOT and SGPT < 3.0 times upper limit of normal (ULN). Subjects with liver
                  metastases may have SGOT/SGPT < 5.0 times ULN.

          -  Women of childbearing potential and male participants must agree to use a medically
             effective means of birth control throughout and for 60 days beyond the treatment phase
             of the study.

          -  Subjects on oral warfarin anticoagulation therapy may be included in this study, but
             must have close monitoring of their coagulation parameters as altered parameters
             and/or bleeding have been reported in patients taking Xeloda® and such agents
             concomitantly. Subjects on other forms of anti-coagulation therapies may need close
             clinical monitoring for signs or symptoms of bleeding.

          -  The subject must possess the ability to give informed consent and express a
             willingness to meet all of the expected requirements of the protocol for the duration
             of the study.

        Exclusion Criteria:

          -  Pregnant and lactating women.

          -  Clinical or laboratory evidence of pancreatitis, based on discretion of treating
             physician.

          -  Serious non-malignant disease (e.g., congestive heart failure or uncontrolled
             infections), which, in the opinion of the investigator would compromise study
             objectives.

          -  Major surgery planned within 3 months of registration other than diagnostic procedures
             such as laparoscopy or endoscopic ultrasound and stenting or PEG/PEJ placement.

          -  Islet cell tumor, benign cyst, peri-ampullary carcinoma or any non-adenocarcinomas.

          -  Acute infection. Acute infection is defined by any viral, bacterial, or fungal
             infection that has required specific therapy within 72 hours of initiation of the
             study therapy (defined as day 1).

          -  Previous history of liver disease including hepatitis.

          -  Positive serologic test for Hepatitis B or C at baseline.

          -  Immunosuppressive therapy including systemic corticosteroids. Use of inhaled and
             topical corticosteroids is permitted.

          -  Impaired immunity or susceptibility to serious viral infections.

          -  Allergy to any product used on the protocol.

          -  Serious medical or psychiatric illness or concomitant medication, which, in the
             judgment of the investigator, might interfere with the subject's ability to respond to
             or tolerate the treatment or complete the trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Toxicity
Time Frame:21 days
Safety Issue:
Description:grade 1 - 5 CTCAE adverse events

Secondary Outcome Measures

Measure:>= grade 3 adverse events
Time Frame:21 days
Safety Issue:
Description:grade 3 - 5 CTCAE adverse events
Measure:PET imaging
Time Frame:14 days
Safety Issue:
Description:HSV-1 TK gene expression via [18F]-FHBG administration and PET imaging

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Henry Ford Health System

Last Updated

September 11, 2017