Description:
This phase 1 trial will investigate the toxicity of combining interleukin 12 gene therapy
with standard chemotherapy in metastatic pancreatic cancer.
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
| Drug | Synonyms | Arms |
|---|
| Ad5-yCD/mutTKSR39rep-hIL12 | | Investigational 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
| Name | Type | Description | Interventions |
|---|
| Investigational Arm | Experimental | Patients 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 13, 2017
