Phase 1 Trial Of Interleukin 12 Gene Therapy For Metastatic Pancreatic Cancer

Study Overview

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

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

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.

Metastatic Pancreatic Cancer

BIOLOGICAL: Ad5-yCD/mutTKSR39rep-hIL12

11260

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2017-09-11	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2022-02-15
First Submitted that Met QC Criteria 2017-09-11	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2022-03-02
First Posted (ACTUAL) 2017-09-13	Results First Posted N/A	Last Verified 2022-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Investigational Arm 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 da	BIOLOGICAL: Ad5-yCD/mutTKSR39rep-hIL12 Oncolytic adenovirus expressing two suicide genes and human IL-12

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Investigational Arm

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 da

BIOLOGICAL: Ad5-yCD/mutTKSR39rep-hIL12

Oncolytic adenovirus expressing two suicide genes and human IL-12

Primary Outcome Measures	Measure Description	Time Frame
Toxicity of the gene therapy	grade 1 - 5 CTCAE adverse events	21 days

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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

Patients

Caregivers

Learn

Resources

Patients

Caregivers

Clinical Trial Record