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Celecoxib in Treating Patients With Cervical Intraepithelial Neoplasia

Primary Purpose

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

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Celecoxib
Laboratory Biomarker Analysis
Placebo
Sponsored by
Gynecologic Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cervical Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of Arizona Cancer Center-North Campus
  • University of Arkansas for Medical Sciences
  • Beebe Medical Center
  • Christiana Care Health System-Christiana Hospital
  • Carle Clinic-Urbana Main
  • Elkhart Clinic
  • Michiana Hematology Oncology PC-Elkhart
  • Elkhart General Hospital
  • Community Howard Regional Health
  • IU Health La Porte Hospital
  • Michiana Hematology Oncology PC-Mishawaka
  • Saint Joseph Regional Medical Center-Mishawaka
  • Michiana Hematology Oncology PC-Plymouth
  • Memorial Hospital of South Bend
  • Michiana Hematology Oncology PC-South Bend
  • Northern Indiana Cancer Research Consortium
  • Michiana Hematology Oncology PC-Westville
  • Union Hospital of Cecil County
  • Borgess Medical Center
  • Bronson Methodist Hospital
  • West Michigan Cancer Center
  • Lakeland Hospital
  • Marie Yeager Cancer Center
  • University of Missouri - Ellis Fischel
  • Saint Louis University Hospital
  • Women's Cancer Center of Nevada
  • Rutgers New Jersey Medical School
  • Montefiore Medical Center - Moses Campus
  • UNC Lineberger Comprehensive Cancer Center
  • Gynecologic Oncology Network
  • FirstHealth of the Carolinas-Moore Regional Hosiptal
  • Wake Forest University Health Sciences
  • University of Cincinnati
  • Case Western Reserve University
  • Hillcrest Hospital Cancer Center
  • Lake University Ireland Cancer Center
  • University of Oklahoma Health Sciences Center
  • Oklahoma Cancer Specialists and Research Institute-Tulsa
  • Sanford USD Medical Center - Sioux Falls
  • Vanderbilt University/Ingram Cancer Center
  • Brooke Army Medical Center
  • Carilion Clinic Gynecological Oncology
  • Froedtert and the Medical College of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (celecoxib)

Arm II (placebo)

Arm Description

Patients receive oral celecoxib once daily for 14-18 weeks.

Patients receive oral placebo once daily for 14-18 weeks.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
April 7, 2004
Last Updated
September 13, 2017
Sponsor
Gynecologic Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00081263
Brief Title
Celecoxib in Treating Patients With Cervical Intraepithelial Neoplasia
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)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gynecologic Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Carcinoma, Cervical Intraepithelial Neoplasia Grade 2/3, Stage 0 Cervical Cancer

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
130 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (celecoxib)
Arm Type
Experimental
Arm Description
Patients receive oral celecoxib once daily for 14-18 weeks.
Arm Title
Arm II (placebo)
Arm Type
Placebo Comparator
Arm Description
Patients receive oral placebo once daily for 14-18 weeks.
Intervention Type
Drug
Intervention Name(s)
Celecoxib
Other Intervention Name(s)
Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-, Celebrex, SC-58635, YM 177
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo therapy, PLCB, sham therapy
Intervention Description
Given orally
Primary Outcome Measure Information:
Title
Histologic Regression
Description
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.
Time Frame
Post treatment evaluation was done 14 to 18 weeks after treatment randomization
Title
Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
Description
Number of participants with a grade of 3 or higher during the treatment period.
Time Frame
Assessed every cycle while on treatment, 30 days after the last cycle of treatment
Other Pre-specified Outcome Measures:
Title
To Examine the Association of Histologic Response in COX-2 in Tissue
Time Frame
Up to 18 weeks
Title
To Examine the Association of Histologic Response in HPV Viral Load in Serum Before and After Treatment
Time Frame
Up to 18 weeks
Title
HPV Viral Load Before and After Treatment
Time Frame
Up to 18 weeks
Title
To Examine the Association of Histologic Response in the Levels of Celecoxib in Serum During Treatment.
Time Frame
Up to 18 weeks
Title
Levels of Serum bFGF
Time Frame
Up to 18 weeks
Title
Levels of Serum VEGF
Time Frame
Up to 18 weeks
Title
To Determine the Feasibility of Digital Imaging Using Pathologist's Diagnosis and Diagnostic Technique (Web-based or Standard Method).
Time Frame
Baseline
Title
To Examine the Association of Histologic Response in Proliferation Index (Ki67).
Time Frame
Up to 18 weeks
Title
Proportion of Patients Whose Eligibility Can be Successfully Determined Using the Web-based Review
Time Frame
Baseline
Title
The Number of Quadrants Involving CIN
Time Frame
Up to 18 weeks
Title
To Examine the Association of Histologic Response in Apoptosis Index (TUNEL Assay)
Time Frame
Up to 18 weeks
Title
To Examine the Association of Histologic Response in Angiogenisis (VEGF)
Time Frame
Up to 18 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janet Rader
Organizational Affiliation
NRG Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arizona Cancer Center-North Campus
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Beebe Medical Center
City
Lewes
State/Province
Delaware
ZIP/Postal Code
19958
Country
United States
Facility Name
Christiana Care Health System-Christiana Hospital
City
Newark
State/Province
Delaware
ZIP/Postal Code
19718
Country
United States
Facility Name
Carle Clinic-Urbana Main
City
Urbana
State/Province
Illinois
ZIP/Postal Code
61801
Country
United States
Facility Name
Elkhart Clinic
City
Elkhart
State/Province
Indiana
ZIP/Postal Code
46514-2098
Country
United States
Facility Name
Michiana Hematology Oncology PC-Elkhart
City
Elkhart
State/Province
Indiana
ZIP/Postal Code
46514
Country
United States
Facility Name
Elkhart General Hospital
City
Elkhart
State/Province
Indiana
ZIP/Postal Code
46515
Country
United States
Facility Name
Community Howard Regional Health
City
Kokomo
State/Province
Indiana
ZIP/Postal Code
46904
Country
United States
Facility Name
IU Health La Porte Hospital
City
La Porte
State/Province
Indiana
ZIP/Postal Code
46350
Country
United States
Facility Name
Michiana Hematology Oncology PC-Mishawaka
City
Mishawaka
State/Province
Indiana
ZIP/Postal Code
46545
Country
United States
Facility Name
Saint Joseph Regional Medical Center-Mishawaka
City
Mishawaka
State/Province
Indiana
ZIP/Postal Code
46545
Country
United States
Facility Name
Michiana Hematology Oncology PC-Plymouth
City
Plymouth
State/Province
Indiana
ZIP/Postal Code
46563
Country
United States
Facility Name
Memorial Hospital of South Bend
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46601
Country
United States
Facility Name
Michiana Hematology Oncology PC-South Bend
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46601
Country
United States
Facility Name
Northern Indiana Cancer Research Consortium
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46628
Country
United States
Facility Name
Michiana Hematology Oncology PC-Westville
City
Westville
State/Province
Indiana
ZIP/Postal Code
46391
Country
United States
Facility Name
Union Hospital of Cecil County
City
Elkton
State/Province
Maryland
ZIP/Postal Code
21921
Country
United States
Facility Name
Borgess Medical Center
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49001
Country
United States
Facility Name
Bronson Methodist Hospital
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
Facility Name
West Michigan Cancer Center
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
Facility Name
Lakeland Hospital
City
Saint Joseph
State/Province
Michigan
ZIP/Postal Code
49085
Country
United States
Facility Name
Marie Yeager Cancer Center
City
Saint Joseph
State/Province
Michigan
ZIP/Postal Code
49085
Country
United States
Facility Name
University of Missouri - Ellis Fischel
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65212
Country
United States
Facility Name
Saint Louis University Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Women's Cancer Center of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
Rutgers New Jersey Medical School
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07101
Country
United States
Facility Name
Montefiore Medical Center - Moses Campus
City
The Bronx
State/Province
New York
ZIP/Postal Code
10467-2490
Country
United States
Facility Name
UNC Lineberger Comprehensive Cancer Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Gynecologic Oncology Network
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
FirstHealth of the Carolinas-Moore Regional Hosiptal
City
Pinehurst
State/Province
North Carolina
ZIP/Postal Code
28374
Country
United States
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Hillcrest Hospital Cancer Center
City
Mayfield Heights
State/Province
Ohio
ZIP/Postal Code
44124
Country
United States
Facility Name
Lake University Ireland Cancer Center
City
Mentor
State/Province
Ohio
ZIP/Postal Code
44060
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Oklahoma Cancer Specialists and Research Institute-Tulsa
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74146
Country
United States
Facility Name
Sanford USD Medical Center - Sioux Falls
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57117-5134
Country
United States
Facility Name
Vanderbilt University/Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Brooke Army Medical Center
City
Fort Sam Houston
State/Province
Texas
ZIP/Postal Code
78234
Country
United States
Facility Name
Carilion Clinic Gynecological Oncology
City
Roanoke
State/Province
Virginia
ZIP/Postal Code
24016
Country
United States
Facility Name
Froedtert and the Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
28285845
Citation
Rader JS, Sill MW, Beumer JH, Lankes HA, Benbrook DM, Garcia F, Trimble C, Tate Thigpen J, Lieberman R, Zuna RE, Leath CA 3rd, Spirtos NM, Byron J, Thaker PH, Lele S, Alberts D. A stratified randomized double-blind phase II trial of celecoxib for treating patients with cervical intraepithelial neoplasia: The potential predictive value of VEGF serum levels: An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol. 2017 May;145(2):291-297. doi: 10.1016/j.ygyno.2017.02.040. Epub 2017 Mar 10.
Results Reference
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Celecoxib in Treating Patients With Cervical Intraepithelial Neoplasia

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