Celecoxib in Treating Patients With Cervical Intraepithelial Neoplasia

Phase 2

Completed

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

Interventions: Drug: Celecoxib
Other: Laboratory Biomarker Analysis
Other: Placebo

Registration Number: NCT00081263

Lead Sponsor: Gynecologic Oncology Group

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 130

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (celecoxib)	Laboratory Biomarker Analysis	Patients receive oral celecoxib once daily for 14-18 weeks.
Arm II (placebo)	Laboratory Biomarker Analysis	Patients receive oral placebo once daily for 14-18 weeks.
Arm II (placebo)	Placebo	Patients receive oral placebo once daily for 14-18 weeks.
Arm I (celecoxib)	Celecoxib	Patients receive oral celecoxib once daily for 14-18 weeks.

Primary Outcome Measures

Name	Time	Method
Histologic Regression	Post treatment evaluation was done 14 to 18 weeks after treatment randomization	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.
Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0	Assessed every cycle while on treatment, 30 days after the last cycle of treatment	Number of participants with a grade of 3 or higher during the treatment period.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (43): Elkhart Clinic
🇺🇸
Elkhart, Indiana, United States
Michiana Hematology Oncology PC-Elkhart
🇺🇸
Elkhart, Indiana, United States
Froedtert and the Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Carilion Clinic Gynecological Oncology
🇺🇸
Roanoke, Virginia, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Michiana Hematology Oncology PC-South Bend
🇺🇸
South Bend, Indiana, United States
Michiana Hematology Oncology PC-Plymouth
🇺🇸
Plymouth, Indiana, United States
Borgess Medical Center
🇺🇸
Kalamazoo, Michigan, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Beebe Medical Center
🇺🇸
Lewes, Delaware, United States
Christiana Care Health System-Christiana Hospital
🇺🇸
Newark, Delaware, United States
Carle Clinic-Urbana Main
🇺🇸
Urbana, Illinois, United States
Elkhart General Hospital
🇺🇸
Elkhart, Indiana, United States
Community Howard Regional Health
🇺🇸
Kokomo, Indiana, United States
IU Health La Porte Hospital
🇺🇸
La Porte, Indiana, United States
Michiana Hematology Oncology PC-Mishawaka
🇺🇸
Mishawaka, Indiana, United States
Saint Joseph Regional Medical Center-Mishawaka
🇺🇸
Mishawaka, Indiana, United States
Memorial Hospital of South Bend
🇺🇸
South Bend, Indiana, United States
Michiana Hematology Oncology PC-Westville
🇺🇸
Westville, Indiana, United States
Union Hospital of Cecil County
🇺🇸
Elkton, Maryland, United States
Bronson Methodist Hospital
🇺🇸
Kalamazoo, Michigan, United States
West Michigan Cancer Center
🇺🇸
Kalamazoo, Michigan, United States
Lakeland Hospital
🇺🇸
Saint Joseph, Michigan, United States
Marie Yeager Cancer Center
🇺🇸
Saint Joseph, Michigan, United States
University of Missouri - Ellis Fischel
🇺🇸
Columbia, Missouri, United States
Saint Louis University Hospital
🇺🇸
Saint Louis, Missouri, United States
Women's Cancer Center of Nevada
🇺🇸
Las Vegas, Nevada, United States
Rutgers New Jersey Medical School
🇺🇸
Newark, New Jersey, United States
Montefiore Medical Center - Moses Campus
🇺🇸
The Bronx, New York, United States
FirstHealth of the Carolinas-Moore Regional Hosiptal
🇺🇸
Pinehurst, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
Hillcrest Hospital Cancer Center
🇺🇸
Mayfield Heights, Ohio, United States
Case Western Reserve University
🇺🇸
Cleveland, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Oklahoma Cancer Specialists and Research Institute-Tulsa
🇺🇸
Tulsa, Oklahoma, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸
Sioux Falls, South Dakota, United States
Brooke Army Medical Center
🇺🇸
Fort Sam Houston, Texas, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
University of Arizona Cancer Center-North Campus
🇺🇸
Tucson, Arizona, United States
Lake University Ireland Cancer Center
🇺🇸
Mentor, Ohio, United States
Gynecologic Oncology Network
🇺🇸
Greenville, North Carolina, United States
Northern Indiana Cancer Research Consortium
🇺🇸
South Bend, Indiana, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸
Chapel Hill, North Carolina, United States