Gene Therapy in Preventing Cancer in Patients With Premalignant Carcinoma of the Oral Cavity or Pharynx

January 22, 2013 updated by: National Cancer Institute (NCI)

Clinical Protocol for Wild Type p53 Gene Induction in Premalignancies of Squamous Epithelium of the Oral Cavity and Oral Pharynx Via an Adenoviral Vector [NCI Supplied Agent Ad-p53, (INGN 201) (Advexin®) NSC 683550, IND# 7135]

This phase I/II trial is studying the side effects and best dose of gene therapy and to see how well it works in preventing cancer in patients with premalignant carcinoma of the oral cavity or pharynx. Inserting the p53 gene into a person's tumor cells may improve the body's ability to kill the tumor cells

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

I. Determine the acute toxic effects of Ad5CMV-p53 gene administered as an oral rinse and as an intramucosal injection in patients with diffuse premalignant carcinoma of the oral cavity or oral pharynx.

II. Determine the maximum tolerated dose of this drug in these patients. III. Determine the topical transduction efficiency of adenoviral-mediated wild type p53 gene transfer in patients treated with this drug.

IV. Determine the efficacy of this drug in reversing the histology of oral premalignancies in these patients.

V. Determine the distribution of transgenic protein within the area of the premalignant lesion in patients treated with this drug.

OUTLINE: This is an open-label, dose-escalation study of Ad5CMV-p53 gene administered as an oral rinse.

Phase I: Patients receive Ad5CMV-p53 gene by intramucosal injection into the area of the lesion followed at least 2 hours later by Ad5CMV-p53 gene as an oral rinse on day 1. Patients then receive Ad5CMV-p53 gene as an oral rinse twice daily on days 2-5. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of Ad5CMV-p53 gene as an oral rinse until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients receive treatment with intramucosal Ad5CMV-p53 gene as in phase I and Ad5CMV-p53 gene as an oral rinse at the MTD. Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years. Patients then receive long-term follow-up annually for an additional 10 years.

Study Type

Interventional

Enrollment (Actual)

51

Phase

  • Phase 2
  • 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
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

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 and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed mild to moderate dysplasia OR severe dysplasia/carcinoma in situ of the oral cavity or oral pharynx

    • Clinically evident diffuse premalignant disease, defined by 1 of the following mucosal abnormalities:

      • Extension between adjacent organ structures (e.g., lateral tongue, ventral tongue, and the floor of the mouth)
      • Extensive surface area, including the entire ventral tongue or floor of the mouth or buccal mucosa, in a velvety "indiscreet" pattern

  • Meets 1 of the following criteria:

    • Previously treated with conventional treatment (e.g., radiotherapy or surgery) for a prior head and neck malignancy
    • Failed biochemoprevention approaches for premalignant disease
    • Failed other therapeutic approaches for premalignant disease
  • No active squamous cell carcinoma of the head and neck
  • Performance status - Karnofsky 70-100%
  • Absolute granulocyte count at least 2,000/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin no greater than 1.0 mg/dL
  • Creatinine no greater than 1.5 mg/dL
  • No hypertension (baseline blood pressure 140/90 mm Hg or higher)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for 1 year after study participation
  • HIV-1 negative
  • No known contact with former tissue or organ transplantation recipients or individuals with severe immunodeficiency disease (acquired or congenital) during and for 28 days after study treatment
  • No prior malignancy within the past 2 years except nonmelanoma skin cancer or aerodigestive cancer
  • No active systemic viral, bacterial, or fungal infections requiring treatment
  • No serious concurrent illness that would preclude study compliance and follow-up
  • No psychological, familial, sociological, geographical, or other condition that would preclude study compliance and follow-up
  • See Disease Characteristics
  • More than 21 days since prior chemotherapy (42 days for mitomycin and nitrosoureas)
  • No concurrent systemic chemotherapy
  • No concurrent prednisone or the equivalent, including corticosteroids of more than 10 mg/day
  • See Disease Characteristics
  • More than 3 months since prior radiotherapy involving the lesion selected for this study
  • No concurrent radiotherapy
  • See Disease Characteristics
  • More than 8 weeks since prior investigational agents
  • No prior experimental therapy (i.e., oral, systemic, topical, or direct injection) for the lesion selected for treatment in this study
  • No other concurrent immunosuppressive therapy
  • No other concurrent investigational agents
  • No concurrent aspirin dose greater than 175 mg/day

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: PREVENTION
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Treatment (Ad5CMV-p53 gene)

Phase I: Patients receive Ad5CMV-p53 gene by intramucosal injection into the area of the lesion followed at least 2 hours later by Ad5CMV-p53 gene as an oral rinse on day 1. Patients then receive Ad5CMV-p53 gene as an oral rinse twice daily on days 2-5. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of Ad5CMV-p53 gene as an oral rinse until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients receive treatment with intramucosal Ad5CMV-p53 gene as in phase I and Ad5CMV-p53 gene as an oral rinse at the MTD.
Other: laboratory biomarker analysis
Correlative studies
Biological: Ad5CMV-p53 gene
Given intramucosally or as oral rinse
Other Names:
  • Ad5CMV-p53
  • ADVEXIN
  • INGN-201

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of adverse events
Time Frame: Up to 15 years
Up to 15 years
Severity of adverse events graded using the CTCAE version 3.0
Time Frame: Up to 15 years
Up to 15 years
Maximum tolerated dose of Ad5CMV-p53 gene
Time Frame: 6 months
Evaluated by the frequency and relationship of dose-limiting toxicities, if any, experienced by patients during dose escalation.
6 months
Pharmacodynamics evaluated by examining the injected precancerous lesion for induction of apoptosis and expression of the p53 protein
Time Frame: 168 days
Presented using descriptive statistics, frequency tabulations, and graphical displays over time by treatment cohort.
168 days

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Gary L. Clayman, M.D. Anderson Cancer Center

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

June 1, 2003

Primary Completion (ACTUAL)

August 1, 2007

Study Registration Dates

First Submitted

July 8, 2003

First Submitted That Met QC Criteria

July 8, 2003

First Posted (ESTIMATE)

July 9, 2003

Study Record Updates

Last Update Posted (ESTIMATE)

January 23, 2013

Last Update Submitted That Met QC Criteria

January 22, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02541
  • MDA-ID-00193
  • P50CA097007 (NIH)
  • CDR0000306522 (REGISTRY: PDQ (Physician Data Query))

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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