Celecoxib in Treating Patients With Cervical Intraepithelial Neoplasia

Cervical Carcinoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00081263
• Other study ID #: GOG-0207
• Secondary ID: NCI-2009-00583CD
• Status: Completed
• Phase: Phase 2
• First received: April 7, 2004
• Last updated: September 13, 2017
• Start date: June 2005

Study information

• Verified date: August 2017
• Source: Gynecologic Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 130
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma in Situ
• Cervical Carcinoma
• Cervical Intraepithelial Neoplasia
• Cervical Intraepithelial Neoplasia Grade 2/3
• Neoplasms
• Stage 0 Cervical Cancer
• Uterine Cervical Dysplasia
• Uterine Cervical Neoplasms

Intervention

Drug:
• Celecoxib
Given orally

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Placebo
Given orally

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Gynecologic Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To Examine the Association of Histologic Response in COX-2 in Tissue		Up to 18 weeks
Other	To Examine the Association of Histologic Response in HPV Viral Load in Serum Before and After Treatment		Up to 18 weeks
Other	HPV Viral Load Before and After Treatment		Up to 18 weeks
Other	To Examine the Association of Histologic Response in the Levels of Celecoxib in Serum During Treatment.		Up to 18 weeks
Other	Levels of Serum bFGF		Up to 18 weeks
Other	Levels of Serum VEGF		Up to 18 weeks
Other	To Determine the Feasibility of Digital Imaging Using Pathologist's Diagnosis and Diagnostic Technique (Web-based or Standard Method).		Baseline
Other	To Examine the Association of Histologic Response in Proliferation Index (Ki67).		Up to 18 weeks
Other	Proportion of Patients Whose Eligibility Can be Successfully Determined Using the Web-based Review		Baseline
Other	The Number of Quadrants Involving CIN		Up to 18 weeks
Other	To Examine the Association of Histologic Response in Apoptosis Index (TUNEL Assay)		Up to 18 weeks
Other	To Examine the Association of Histologic Response in Angiogenisis (VEGF)		Up to 18 weeks
Primary	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
Primary	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