Study Combining Suicide Gene Therapy With Chemoradiotherapy in the Treatment of Non-Metastatic Pancreatic Adenocarcinoma

June 21, 2011 updated by: Henry Ford Health System

Phase I Study Combining Replication-Competent Adenovirus-Mediated Suicide Gene Therapy With Chemoradiotherapy for the Treatment of Non-Metastatic Pancreatic Adenocarcinoma

The primary purpose of this phase I study is to determine the safety of combining replication-competent adenovirus-mediated suicide gene therapy with chemoradiotherapy in patients with non-metastatic pancreatic cancer.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The objectives of this study are:

To determine the toxicity and maximum tolerated dose (MTD) of the Ad5-yCD/mutTKSR39rep-ADP adenovirus in combination with 5-fluorocytosine (5-FC) and valganciclovir (vGCV) prodrug therapy and standard chemoradiation. Fifteen to 30 subjects (5 cohorts of 3 - 6 subjects each) with non-metastatic, unresectable pancreatic cancer will receive a single intratumoral injection of the Ad5-yCD/mutTKSR39rep-ADP adenovirus at one of five dose levels (1 x 10e10 vp, 3 x 10e10 vp, 1 x 10e11 vp, 3 x 10e11 vp, 1 x 10e12 vp) under endoscopic ultrasound (EUS)-guidance. Beginning three days later, subjects will receive 3 weeks (15 days) of 5-FC and vGCV prodrug therapy concomitant with a 6 week (30 day) course of capecitabine chemotherapy and 54 Gy conformal radiotherapy.

The primary endpoint is toxicity at 12 weeks. Secondary endpoints are: 1) tumor (radiological) response, 2) time to disease progression, 3) survival, 4) persistence of Ad5-yCD/mutTKSR39rep-ADP adenoviral DNA in blood, 5) infectious Ad5-yCD/mutTKSR39rep-ADP adenovirus in blood, and 6) HSV-1 TK gene expression in the pancreas.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System

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.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age > = 18 and < = 80.
  • Non-metastatic, unresectable tumors
  • No evidence of peritoneal and/or hematogenous metastasis.
  • Histologically proven (biopsy or cytology) adenocarcinoma.
  • No evidence of peritoneal and/or hematogenous metastasis.
  • No prior chemotherapy, radiotherapy or biological therapy.
  • ECOG performance status 0 - 2.
  • 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 <=1.5 mg/dL or creatinine clearance >=50 mL/min/m2.
  • Absolute WBC > 4,000/μL.
  • Hemoglobin > 9.0 g/dL.
  • Platelet count > 100,000/μL.
  • Bilirubin < 1.5 mg/dL; SGOT and SGPT < 2.5 times upper limit of normal (ULN).
  • No history of malignancy within 5 years except for non-melanomatous skin cancer or carcinoma in situ of the cervix.
  • Men and women with conceptive potential must agree to follow a medically acceptable method of birth control.
  • Patients 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.
  • 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.
  • 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 within four weeks other than diagnostic procedures such as laparoscopy, 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).
  • Active HIV disease.
  • 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.
  • 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.
  • Impaired immunity or susceptibility to serious viral infections.
  • Allergy to any product used on the protocol including ciprofloxacin.
  • Clinical or laboratory evidence of pancreatitis

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Gene therapy
Adenovirus injection followed by 3 weeks of 5-FC + vGCV prodrug therapy and a 6 week course of capecitabine-based chemoradiation
Genetic: Ad5-yCD/mutTKSR39rep-ADP
Single injection on day 1 at one of five dose levels

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Toxicity
Time Frame: 12 weeks post adenovirus injection
12 weeks post adenovirus injection

Secondary Outcome Measures

Outcome Measure
Time Frame
Tumor response
Time Frame: 3 - 12 months
3 - 12 months
Time to progression
Time Frame: 3 - 12 months
3 - 12 months
Survival
Time Frame: 10 - 20 months
10 - 20 months
Gene expression in pancreas
Time Frame: 1 - 14 days
1 - 14 days

Collaborators and Investigators

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

Sponsor

Henry Ford Health System

Investigators

  • Principal Investigator: Munther Ajlouni, M.D., Henry Ford Health System

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 Major Dates

Study Start

November 1, 2006

Study Registration Dates

First Submitted

December 21, 2006

First Submitted That Met QC Criteria

December 21, 2006

First Posted (ESTIMATE)

December 25, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

June 23, 2011

Last Update Submitted That Met QC Criteria

June 21, 2011

Last Verified

June 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Panc4242
  • P01CA097012 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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