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

PHASE 1 TRIAL OF ONCOLYTIC ADENOVIRUS-MEDIATED CYTOTOXIC AND IL-12 GENE THERAPY IN COMBINATION WITH CHEMOTHERAPY FOR THE TREATMENT OF METASTATIC PANCREATIC CANCER

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

Study Overview

• Status: Completed
• Conditions: Metastatic Pancreatic Cancer
• Intervention / Treatment: Biological: Ad5-yCD/mutTKSR39rep-hIL12

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

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 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.

Biological: Ad5-yCD/mutTKSR39rep-hIL12; Oncolytic adenovirus expressing two suicide genes and human IL-12

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Henry Ford Health System

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Actual): May 28, 2019
• Study Completion (Actual): May 28, 2019

Study Registration Dates

• First Submitted: September 11, 2017
• First Submitted That Met QC Criteria: September 11, 2017
• First Posted (Actual): September 13, 2017

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 15, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: 11260

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No