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

This study has been terminated.
(Poor enrollment)
Sponsor:
Information provided by:
Henry Ford Health System
ClinicalTrials.gov Identifier:
NCT00415454
First received: December 21, 2006
Last updated: June 21, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention Phase
Pancreatic Cancer
Genetic: Ad5-yCD/mutTKSR39rep-ADP
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study Combining Replication-Competent Adenovirus-Mediated Suicide Gene Therapy With Chemoradiotherapy for the Treatment of Non-Metastatic Pancreatic Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Henry Ford Health System:

Primary Outcome Measures:
  • Toxicity [ Time Frame: 12 weeks post adenovirus injection ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumor response [ Time Frame: 3 - 12 months ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: 3 - 12 months ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: 10 - 20 months ] [ Designated as safety issue: No ]
  • Gene expression in pancreas [ Time Frame: 1 - 14 days ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: November 2006
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00415454

Locations
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
Sponsors and Collaborators
Henry Ford Health System
Investigators
Principal Investigator: Munther Ajlouni, M.D. Henry Ford Health System
  More Information

No publications provided

Responsible Party: Svend O. Freytag, Ph.D., Henry Ford Health System
ClinicalTrials.gov Identifier: NCT00415454     History of Changes
Other Study ID Numbers: Panc4242, P01 CA097012
Study First Received: December 21, 2006
Last Updated: June 21, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Henry Ford Health System:
Pancreatic Cancer

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Suicide
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Self-Injurious Behavior
Behavioral Symptoms

ClinicalTrials.gov processed this record on August 01, 2014