Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Prevention Completed 18 and over NCI MDA-ID-00193 NCI-6053, NCT00064103, 6053

Objectives

1. 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.
2. Determine the maximum tolerated dose of this drug in these patients.
3. Determine the topical transduction efficiency of adenoviral-mediated wild type p53 gene transfer in patients treated with this drug.
4. Determine the efficacy of this drug in reversing the histology of oral premalignancies in these patients.
5. Determine the distribution of transgenic protein within the area of the premalignant lesion in patients treated with this drug.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• More than 21 days since prior chemotherapy (42 days for mitomycin and nitrosoureas)
• No concurrent systemic chemotherapy

Endocrine therapy

• No concurrent prednisone or the equivalent, including corticosteroids of more than 10 mg/day

Radiotherapy

• See Disease Characteristics
• More than 3 months since prior radiotherapy involving the lesion selected for this study
• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• 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

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count at least 2,000/mm³
• Platelet count at least 100,000/mm³

Hepatic

• Bilirubin no greater than 1.0 mg/dL

Renal

• Creatinine no greater than 1.5 mg/dL

Cardiovascular

• No hypertension (baseline blood pressure 140/90 mm Hg or higher)

Other

• 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

Expected Enrollment

A total of 18-51 patients (18 for phase I and 33 for phase II) will be accrued for this study.

Outcomes

Safety at weeks 2-4 and then for 6 months
Maximum tolerated dose of Ad5CMV-p53 gene administered as an oral rinse at weeks 2-4 and then for 6 months
Transduction and efficiency of treatment as measured by Simon's optimal 2-stage design at weeks 2-4 and then for 6 months

Effect of p53 gene transfer on molecular biomarkers of p53 activity reduction as measured by immunohistochemical staining at baseline and during courses 1 and 6

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.

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

Gary L. Clayman, MD, DDS, Protocol chair		Ph: 713-792-6525; 800-392-1611 Email: gclayman@mdanderson.org
Scott Lippman, MD, FACP, Protocol co-chair		Ph: 713-745-5439; 800-392-1611

Registry Information
Official Title		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]
Trial Start Date		2006-06-25
Registered in ClinicalTrials.gov		NCT00064103 1
Date Submitted to PDQ		2003-05-20
Information Last Verified		2007-01-25
NCI Grant/Contract Number		CA97007, CA16672

Table of Links

1	http://clinicaltrials.gov/ct/show/NCT00064103