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 CIN 3)
18 Years
N/A
Female
Cervical Cancer, Precancerous Condition
Trial Information
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 CIN 3)
OBJECTIVES:
Primary
- Determine the efficacy of celecoxib, in terms of achieving histologic complete or
partial response, in patients with cervical intraepithelial neoplasia (CIN) 2/3 or 3.
- Determine the toxicity of this drug in these patients.
Secondary
- Determine the effect of this drug on changes in lesion size in these patients.
- Determine the effect of this drug on human papillomavirus (HPV) viral load in these
patients.
- Correlate histologic response, HPV viral load, lesion size, proliferation index,
apoptosis index, angiogenesis (VEGF) and COX-2 in tissue, amount of VEGF and bFGF in
serum, and serum celecoxib levels during treatment in these patients.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to lesion size (covering ≤ ½ area of the cervix vs covering > ½
area of the cervix) and degree of cervical intraepithelial neoplasia (CIN) (CIN 2/3 vs CIN
3). 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. Patients undergo
colposcopy at week 8 and between weeks 14 and 18. Between weeks 14 and 18, patients
with evidence of disease also undergo large loop excision of the transformation zone
(cone biopsy) or cervical biopsy and patients with no evidence of disease undergo a
cervical biopsy to confirm the absence of disease on colposcopy.
PROJECTED ACCRUAL: A maximum of 130 patients (39 per treatment arm) will be accrued for this
study within 13 months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed cervical intraepithelial neoplasia (CIN) 2/3 or 3 by
cervical biopsy 2-8 weeks prior to study entry
- Pathology report must clearly state "CIN 2/3" or "3" OR "moderate-severe
dysplasia," "moderate-severe dyskaryosis," "severe dysplasia," or "sever
dyskaryosis."
- No CIN 2 alone OR moderate dysplasia or dyskaryosis alone
- Colposcopically visible cervical lesion at study entry that is consistent with biopsy
- No evidence of endocervical dysplasia or invasive cancer by cytology or biopsy
- No history of cervical cancer
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- GOG 0-2
Life expectancy
- Not specified
Hematopoietic
- Platelet count > 125,000/mm^3
- Hemoglobin > 11.0 g/dL
- WBC > 3,000/mm^3
- No significant bleeding disorder
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN) (> 1.5 times ULN allowed if due to
Gilbert's disease)
- AST and ALT < 2.0 times ULN
- No hepatic disorder
Renal
- Creatinine ≤ 1.5 times ULN
- No known renal failure
Cardiovascular
- No history of transient ischemic attack or stroke
- No history of cardiovascular disease
- No uncontrolled hypertension
Other
- No undiagnosed abnormal vaginal bleeding
- No known immunocompromised condition
- No known allergic reaction (such as asthma, urticaria, or other reaction) to NSAIDs
or aspirin
- No known hypersensitivity to celecoxib
- No known allergic reaction to sulfonamides
- No history of peptic ulcer disease
- Must be good candidate for delayed treatment of CIN (i.e., deemed reliable to return
for follow-up and provide adequate contact information)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- Not specified
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- No prior renal transplantation
Other
- At least 15 days since prior nonsteriodal anti-inflammatory agents (NSAIDs) or
aspirin
- No other concurrent NSAIDs or aspirin
- No concurrent fluconazole or lithium
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention
Outcome Measure:
Histologic complete response
Safety Issue:
No
Principal Investigator
Janet S. Rader, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Washington University Siteman Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000360805
NCT ID:
NCT00081263
Start Date:
June 2005
Completion Date:
Related Keywords:
- Cervical Cancer
- Precancerous Condition
- cervical cancer
- cervical intraepithelial neoplasia grade 2
- cervical intraepithelial neoplasia grade 3
- Neoplasms
- Uterine Cervical Neoplasms
- Precancerous Conditions
- Cervical Intraepithelial Neoplasia
- Carcinoma in Situ
Name | Location |
|---|---|
| CCOP - Christiana Care Health Services | Wilmington, Delaware 19899 |
| Bronson Methodist Hospital | Kalamazoo, Michigan 49007 |
| West Michigan Cancer Center | Kalamazoo, Michigan 49007-3731 |
| Borgess Medical Center | Kalamazooaa, Michigan 49001 |
| Sanford Cancer Center at Sanford USD Medical Center | Sioux Falls, South Dakota 57117-5039 |
| Medical College of Wisconsin Cancer Center | Milwaukee, Wisconsin 53226 |
| Memorial Hospital of South Bend | South Bend, Indiana 46601 |
| CCOP - Northern Indiana CR Consortium | South Bend, Indiana 46601 |
| Saint Joseph Regional Medical Center | South Bend, Indiana 46617 |
| Charles M. Barrett Cancer Center at University Hospital | Cincinnati, Ohio 45267-0526 |
| Arkansas Cancer Research Center at University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
| Oklahoma University Cancer Institute | Oklahoma City, Oklahoma 73104 |
| Elkhart General Hospital | Elkhart, Indiana 46515 |
| Howard Community Hospital | Kokomo, Indiana 46904 |
| Lakeland Regional Cancer Care Center - St. Joseph | St. Joseph, Michigan 49085 |
| Cancer Care Associates - Saint Francis Campus | Tulsa, Oklahoma 74136-1929 |
| Center for Cancer Therapy at LaPorte Hospital and Health Services | La Porte, Indiana 46350 |
| Michiana Hematology-Oncology, PC - Elkhart | Elkhart, Indiana 46514 |
| Elkhart Clinic, LLC | Elkhart, Indiana 46514-2098 |
| Michiana Hematology Oncology PC - La Porte | La Porte, Indiana 46350 |
| Michiana Hematology-Oncology, PC - South Bend | Mishawaka, Indiana 46545-1470 |
| Michiana Hematology Oncology PC - Plymouth | Plymouth, Indiana 46563 |
| Lakeside Cancer Specialists, PLLC | Saint Joseph, Michigan 49085 |
| FirstHealth Moore Regional Community Hospital Comprehensive Cancer Center | Pinehurst, North Carolina 28374 |
| Women's Cancer Center - La Canada | Las Vegas, Nevada 89169 |
