Wild Type p53 Adenovirus for Oral Premalignancies

NCT00410865 | Terminated Phase 1 DMC

• 1 other identifier: ID00-193
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objectives:

1. 1.To determine the maximum tolerated dose and transduction efficiency of adenoviral mediated wild type p53 gene transfer in premalignancies of the upper aerodigestive tract.
2. 2.To determine the efficacy of single agent adenoviral mediated wild type p53 gene transfer in reversing oral premalignancies.

Conditions

Mouth Cancer

Keywords

Oral Premalignancies; Mouth Cancer; Dysplasia/Carcinoma in Situ (CIS) of the Oral Cavity; Dysplasia/Carcinoma in situ (CIS) of the Oral Pharynx; Advexin; Gene Therapy; INGN 201; Wild Type p53 Gene Induction

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of INGN 201

  MTD is defined as the highest dose level at which there are less than or equal to 1/6 patients with a dose limiting toxicity (DLT).

  Following 1 week of experimental treatment in each 4 week course

Study Arms (1)

INGN 201

EXPERIMENTAL

INGN201 injection + oral rinse, day 1, courses 1-6. Twice-daily oral rinses, days 2-5, courses 1-6.

Genetic: INGN 201

Interventions

INGN 201 GENETIC

Mouth rinse given one time on the first day and two times on Days 2-5 of each course of INGN 201. The injection and rinse (first day of each cycle), or the two rinses (Days 2-5 of each cycle), will be separated by at least two hours.

Also known as: Advexin, Ad-p53

INGN 201

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females, aged 18 years and older.
• Patients must have histologically confirmed diagnosis of mild-moderate dysplasia or severe dysplasia/carcinoma in situ (CIS) of the oral cavity or oral pharynx.
• Patients must have clinical evidence of mild to moderate dysplasia or severe dysplasia/CIS of the oral cavity or oral pharynx that is diffuse.
• Patients must have diffuse\* premalignant disease of the oral cavity or oral pharynx and must have: a) been previously treated with conventional treatment (e.g.: radiation or surgery) for a prior head \& neck malignancy or b) failed biochemoprevention approaches for premalignant disease or c) failed other therapeutic approaches for premalignant disease. (\*See protocol for definition of diffuse.)
• All patients must have a Karnofsky performance status of greater than or equal to 70% (Karnofsky scale, Appendix B).
• All patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of the institution.
• If female and of childbearing potential (non-childbearing defined as 1 year post menopause or surgically sterilized), patients must have a negative serum pregnancy test. Patients (male and female) must agree to use barrier contraception while on study and to avoid pregnancy for 1 year after treatment.
• Patients must have negative serology for the Human Immunodeficiency Virus (HIV) Type I. (Safety of the product has not been established or studied in immunosuppressed populations).
• Patients must have adequate bone marrow function (defined as peripheral absolute granulocyte count of greater than or equal to 2,000/ul and platelet count of greater than or equal to 100,000/ul), adequate liver function (bilirubin less than or equal to 1.0 mg/dl), and adequate renal function (creatinine less than or equal to 1.5 mg/dl).
• Patients must not knowingly be in contact with former tissue or organ transplant recipients and persons known to them to be suffering from severe immunodeficiency disease (either acquired or congenital) during treatment or within 28 days following the last dosing with Ad5CMV p53 (INGN 201).

You may not qualify if:

• Active squamous cell carcinoma of the head and neck.
• History of prior malignancies (excluding non-melanoma skin cancers and aerodigestive cancers) unless curatively treated and disease free for greater than or equal to 2 years.
• Prior experimental therapy oral, systemic, topical, or directly injected into the lesion selected for treatment in this study, or radiation directly involving the lesion selected in the last three (3) months.
• Chemotherapy within 21 days prior to study (42 days for mitomycin C and nitrosoureas).
• Pregnant or lactating females. (Transplacental transfer and excretion in breast milk have not been studied with this agent).
• Active systemic viral, bacterial, or fungal infections requiring treatment.
• Patients with serious concurrent illness of psychological, familial, sociological, geographical or other concomitant conditions which do not allow for adequate follow up and compliance with the study protocol.
• Concurrent use of other investigational agents.
• Prior use of any other investigational agent requires a washout period of 8 weeks.
• Any immunosuppressive therapy (including corticosteroids \> 10 mg/day) of prednisone or the equivalent.
• Aspirin use in an average dose of \>175 mg/d.
• Patients evaluated by Internal Medicine with a baseline blood pressure of \> or equal to 140/90 and deemed hypertensive.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Department of Health and Human Services: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center

MeSH Terms

Conditions

Mouth Neoplasms; Carcinoma in Situ

Interventions

advexin

Condition Hierarchy (Ancestors)

Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Gary L. Clayman, MD

  U.T. MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2006
• First Posted: December 13, 2006
• Study Start: June 1, 2003
• Primary Completion: March 1, 2008
• Study Completion: November 1, 2010
• Last Updated: December 7, 2011

Record last verified: 2011-12

Locations

US (1)