S0212 Celecoxib in Treating Patients With High-Grade Squamous Intraepithelial Lesions of the Cervix

S0212: Phase IIb Randomized Study of Celecoxib in Patients With High-Grade Squamous Intraepithelial Lesions of the Cervix

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. Celecoxib may be effective in preventing cervical cancer.

PURPOSE: Randomized phase II trial to study the effectiveness of celecoxib in preventing cervical cancer in patients who have high-grade squamous intraepithelial lesions of the cervix.

OBJECTIVES:

• Compare the complete response rate in patients with high-grade squamous intraepithelial lesions of the cervix treated with celecoxib vs placebo.
• Compare the toxicity of these drugs in these patients.
• Determine, preliminarily, the effect of celecoxib on cyclooxygenase-2 expression and human papilloma virus expression in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to high-grade squamous intraepithelial lesion status (cervical intraepithelial neoplasia [CIN] 2 vs CIN 3). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral celecoxib twice daily for 1 month.
• Arm II: Patients receive oral placebo twice daily for 1 month. In both arms, treatment repeats monthly for 3 courses in the absence of disease progression or unacceptable toxicity. All patients then undergo loop electrosurgical excision procedure or cone biopsy to determine response.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study within 1-2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed high-grade squamous intraepithelial lesions (HGSIL) of the cervix
• Cervical intraepithelial neoplasia (CIN) 2 (moderate dysplasia) OR CIN 3 (severe dysplasia, carcinoma in situ)
• Must have remaining HGSIL after biopsy
• No suspicion of invasive cancer by colposcopy within the past 28 days
• No invasive or preinvasive high-grade intraepithelial neoplasia by endocervical curettage within the past 56 days

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• SGOT and SGPT less than 2.0 times upper limit of normal (ULN)
• Bilirubin less than 2.0 times ULN

Renal

• Creatinine less than 2.0 mg/dL

Immunologic

• No prior asthma, urticaria, or allergic-type reactions to aspirin or other NSAIDs
• No allergy to sulfonamides
• No known sensitivity to celecoxib
• No known AIDS or HIV-associated complex

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or adequately treated stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• No prior pelvic radiotherapy

Surgery

• See Disease Characteristics

Other

• More than 3 months since prior topical medications for genital condyloma
• No prior treatment for squamous intraepithelial lesions
• No concurrent topical medications for genital condyloma
• No other concurrent treatment
• No concurrent chronic (daily for more than 30 days) aspirin
• No other concurrent nonsteroidal anti-inflammatory drugs (NSAIDs)