Gene Therapy in Preventing Cancer in Patients With Premalignant Carcinoma of the Oral Cavity or Pharynx - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00064103

Purpose

RATIONALE: Inserting the p53 gene into a person's tumor cells may improve the body's ability to kill the tumor cells.

PURPOSE: 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.

Condition	Intervention	Phase
Head and Neck Cancer	Biological: Ad5CMV-p53 gene	Phase I Phase II

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Prevention
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]

Resource links provided by NLM:

Genetics Home Reference related topics: Li-Fraumeni syndrome Help Me Understand Genetics

MedlinePlus related topics: Cancer Head and Neck Cancer

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety at weeks 2-4 and then for 6 months [ Designated as safety issue: Yes ]
Maximum tolerated dose of Ad5CMV-p53 gene administered as an oral rinse at weeks 2-4 and then for 6 months [ Designated as safety issue: Yes ]
Transduction and efficiency of treatment as measured by Simon's optimal 2-stage design at weeks 2-4 and then for 6 months [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 [ Designated as safety issue: No ]

Estimated Enrollment:	51
Study Start Date:	June 2006

Detailed Description:

OBJECTIVES:

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.
Determine the maximum tolerated dose of this drug in these patients.
Determine the topical transduction efficiency of adenoviral-mediated wild type p53 gene transfer in patients treated with this drug.
Determine the efficacy of this drug in reversing the histology of oral premalignancies in these patients.
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.

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

Karnofsky 70-100%

Life expectancy

Not specified

Hematopoietic

Absolute granulocyte count at least 2,000/mm^3
Platelet count at least 100,000/mm^3

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00064103

Locations

United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, Texas
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:	Gary L. Clayman, MD, DDS	M.D. Anderson Cancer Center
Investigator:	Scott M. Lippman, MD, FACP	M.D. Anderson Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00064103 History of Changes
Other Study ID Numbers:	CDR0000306522, MDA-ID-00193, NCI-6053
Study First Received:	July 8, 2003
Last Updated:	March 2, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

lip and oral cavity cancer
oropharyngeal cancer
tongue cancer
stage 0 lip and oral cavity cancer
stage 0 oropharyngeal cancer

Additional relevant MeSH terms:

Head and Neck Neoplasms
Neoplasms by Site
Neoplasms

ClinicalTrials.gov processed this record on February 09, 2012