PHASE 1 TRIAL OF ONCOLYTIC ADENOVIRUS-MEDIATED CYTOTOXIC AND IL-12 GENE THERAPY IN COMBINATION WITH CHEMOTHERAPY FOR THE TREATMENT OF METASTATIC PANCREATIC CANCER
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Metastatic Pancreatic Cancer
- Sponsor
- Henry Ford Health System
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Toxicity of the gene therapy
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
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.
Investigators
David Kwon, MD
Medical Director, Center for Cancer Surgery
Henry Ford Health System
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/m
- •Absolute neutrophil count \> 1,000/μL.
- •Hemoglobin \> 8.0 g/dL.
- •Platelet count \> 100,000/μL.
- •Bilirubin \< 2.0 mg/dL.
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.
Outcomes
Primary Outcomes
Toxicity of the gene therapy
Time Frame: 21 days
grade 1 - 5 CTCAE adverse events
Secondary Outcomes
- PET imaging(14 days)
- >= grade 3 adverse events(21 days)