Celecoxib in Treating Patients With Cervical Intraepithelial Neoplasia

Study Overview
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Brief Summary
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This randomized phase II trial studies how well celecoxib works in treating patients with cervical intraepithelial neoplasia, a precancerous lesion of the cervix which can develop into cervical cancer. Celecoxib may be effective in preventing the development of cervical cancer in patients who have cervical intraepithelial neoplasia.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the efficacy of celecoxib to induce complete remission (or partial regression to cervical intraepithelial neoplasia (CIN) 1) of CIN 2/3 or CIN 3 as evaluated in the post-treatment excisional biopsy. II. To determine the toxicity of celecoxib (400 mg once daily) as assessed by Common Terminology Criteria for Adverse Events in this patient population of women with CIN 2/3 or CIN 3. SECONDARY OBJECTIVES: I. To assess whether treatment with celecoxib changes the number of quadrants containing acetowhite lesions as determined through colposcopic examination. II. To determine the efficacy of celecoxib treatment in changing human papillomavirus (HPV) viral load in cervical cells. III. To examine the association of histologic response; HPV viral load; lesion size; proliferation index (marker of proliferation Ki-67 [Ki67]), apoptosis index (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labelin [TUNEL] assay), angiogenesis (vascular endothelial growth factor [VEGF]), and cyclooxygenase-2 (COX-2) in tissue; the amount of VEGF and basic fibroblast growth factor (bFGF) in serum before and after treatment; and the amount of celecoxib present in serum during treatment. Cervical cytology karyometry will be assessed as a potential marker for regression IV. To determine the feasibility of digital imaging, web-based review of histopathology in a Gynecologic Oncology Group (GOG) study. V. To compare the diagnoses of the web-based review of histopathology with the diagnoses of GOG's standard procedure. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive oral celecoxib once daily for 14-18 weeks. ARM II: Patients receive oral placebo once daily for 14-18 weeks.

Official Title
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A Randomized Double-Blind Phase II Trial of Celecoxib, A COX-2 Inhibitor, in the Treatment of Patients With Cervical Intraepithelial Neoplasia 2/3 or 3 (CIN 2/3 or 3)

Conditions
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Cervical Carcinoma, Cervical Intraepithelial Neoplasia Grade 2/3, Stage 0 Cervical Cancer

Intervention / Treatment
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* Drug: Celecoxib
* Other: Laboratory Biomarker Analysis
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically proven CIN 2/3 or CIN 3 diagnosed by cervical biopsy between 2 and 8 weeks prior to enrollment For a patient to be eligible, the pathology report must clearly state CIN 2/3 or CIN 3 or must state moderate-severe dysplasia, moderate-severe dyskaryosis, severe dysplasia, or severe dyskaryosis; patients with a diagnosis of CIN 2 alone or moderate dysplasia or dyskaryosis alone are not eligible for this study (3/26/2007) Patients must have a satisfactory (readable, good quality) colposcopic evaluation at least 14 days after diagnostic biopsy Patients must have signed an approved informed consent and authorization permitting release of personal health information Patients must have colposcopically visible cervical lesion at entry consistent with biopsy Patients must have a negative urine pregnancy test; women of childbearing potential must practice an acceptable form of contraception (e.g. intrauterine device, contraceptive pills, diaphragm, condoms) Patients must have a GOG Performance Status of 0, 1, or 2 Patients must agree to refrain from using non-steroidal anti-inflammatory drugs (NSAIDS) and aspirin during the time they are taking the study medication Patients must be good candidates for delayed treatment of their CIN, i.e. they must be reliable to return for follow-up and provide a combination of at least three phone numbers or addresses for contact Hemoglobin (HgB) greater than 11.0g/dl White blood cell (WBC) count greater than 3000/mcl Platelet count greater than 125,000/mcl (3/26/2007) Creatinine less than or equal to 1.5 x upper limit normal (ULN) Total bilirubin less than or equal to 1.5 x ULN excluding Gilbert's disease Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.0 x ULN Exclusion Criteria: Patients who are pregnant or lactating Patients with cytologic or biopsy evidence of endocervical dysplasia or invasive cancer Patients with undiagnosed abnormal vaginal bleeding Patients who have previously taken celecoxib or any other COX-2 inhibitor at a frequency of greater than 3 times per week within 2 months (60 days) prior to randomization; patients can use Naproxen without restriction (6/23/2008) Patients with a known immunocompromised condition Patients who have had a known allergic reaction to any NSAIDS or aspirin (asthma, urticaria, allergic-type reaction) Patients with a prior history of cervical cancer Patients with hypersensitivity to Celecoxib Patients with a known allergic reaction to sulfonamides Patients with a history of peptic ulcer disease Patients currently using fluconazole or lithium Patients with a chronic or acute renal, or hepatic disorder, a significant bleeding disorder, or any other condition which in the investigator's opinion might preclude study participation for the duration of the trial Patients with a history of transient ischemic attack (TIA), stroke, cardiovascular disease or uncontrolled hypertension

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (celecoxib)<br>Patients receive oral celecoxib once daily for 14-18 weeks. | Drug: Celecoxib<br>* Given orally<br>* Other names: YM 177;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|
| Placebo Comparator: Arm II (placebo)<br>Patients receive oral placebo once daily for 14-18 weeks. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Placebo<br>* Given orally<br>* Other names: sham therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histologic Regression | Whether or not patients with CIN 2/3 or CIN 3 upon entry experience a complete remission (or partial regression to CIN 1) in the post-treatment excisional biopsy. | Post treatment evaluation was done 14 to 18 weeks after treatment randomization | 
| Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Number of participants with a grade of 3 or higher during the treatment period. | Assessed every cycle while on treatment, 30 days after the last cycle of treatment |