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

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ClinicalTrials.gov Identifier: NCT03281382
Recruitment Status : Recruiting
First Posted : September 13, 2017
Last Update Posted : September 13, 2017
Sponsor:
Information provided by (Responsible Party):
David Kwon, MD, Henry Ford Health System

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

Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Cancer Biological: Ad5-yCD/mutTKSR39rep-hIL12 Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 1, 2017
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Toxicity [ Time Frame: 21 days ]
    grade 1 - 5 CTCAE adverse events


Secondary Outcome Measures :
  1. >= grade 3 adverse events [ Time Frame: 21 days ]
    grade 3 - 5 CTCAE adverse events

  2. PET imaging [ Time Frame: 14 days ]
    HSV-1 TK gene expression via [18F]-FHBG administration and PET imaging



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03281382


Contacts
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Contact: David Kwon, MD 3139169930 dkwon1@hfhs.org
Contact: Janice Freytag, BS 3138748326 jfreyta1@hfhs.org

Locations
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United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: David Kwon, MD    313-916-9930    dkwon1@hfhs.org   
Contact: Janice Freytag, BS    3138748236    jfreyta1@hfhs.org   
Sponsors and Collaborators
Henry Ford Health System

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Responsible Party: David Kwon, MD, Medical Director, Center for Cancer Surgery, Henry Ford Health System
ClinicalTrials.gov Identifier: NCT03281382     History of Changes
Other Study ID Numbers: 11260
First Posted: September 13, 2017    Key Record Dates
Last Update Posted: September 13, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases