CA-IX, p16, Proliferative Markers, and HPV in Diagnosing Cervical Lesions in Patients With Abnormal Cervical Cells

Human Papillomavirus Infection Clinical Trial

Official title:

Comparative Analysis of CA-IX, p16, Proliferative Markers, and Human Papilloma Virus (HPV) in the Diagnosis of Significant Cervical Lesions in Patients With a Cytologic Diagnosis of Atypical Glandular Cells (AGC)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00892866
• Other study ID #: GOG-0237
• Secondary ID: NCI-2009-01103CD
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 13, 2009
• Est. completion date: May 31, 2025

Study information

• Verified date: May 2024
• Source: GOG Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research trial studies carbonic anhydrase 9 (CA-IX), p16, proliferative markers, and human papilloma virus (HPV) in diagnosing cervical lesions in patients with abnormal cervical cells. Studying biomarkers in abnormal cervical cells may improve the ability to find cervical lesions and plan effective treatment.

Description:

PRIMARY OBJECTIVES:

I. To examine CA-IX, p16, Ki-67, and mini-chromosome maintenance complex component 2 (MCM2) expression in liquid-based cytology (LBC) specimens to see which subset of markers can provide the optimal diagnosis of significant cervical lesions in women in North America with a cytologic diagnosis of atypical glandular cells (AGC) and a positive test for high risk human papillomavirus (HPV).

II. To examine high risk HPV, CA-IX, p16, Ki-67, and MCM2 expression in LBC specimens to see which subset of markers can provide the optimal diagnosis of significant cervical lesions in women in Japan and Korea (with each country's cohort analyzed separately) with a cytologic diagnosis of AGC.

SECONDARY OBJECTIVES:

I. To determine whether the accuracy of diagnosis based on high risk HPV and expression of CA-IX, p16, Ki-67, and/or MCM2 varies with patient age at enrollment and country of enrollment.

TERTIARY OBJECTIVES:

I. To assess biomarker expression, loss of heterozygosity, and chromosome gains/losses in formalin-fixed, paraffin-embedded tissue from the highest grade or most abnormal lesion in women from North America, Japan, or Korea presenting with a cytologic diagnosis of AGC or with a cytologic/histologic diagnosis of adenocarcinoma in situ (AIS).

II. To determine CA-IX, p16, Ki67, and MCM2 expression in LBC specimens to see which subset (or combination) of markers will provide higher sensitivity in the diagnosis of cervical adenocarcinoma in situ (AIS).

OUTLINE:

Patients undergo liquid-based cytology specimen sample collection for analysis of CA-IX, p16, Ki-67, and MCM2 expression via immunohistochemistry (IHC) and for the presence of high risk HPV deoxyribonucleic acid (DNA) and HPV genotyping.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 877
• Est. completion date: May 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with a cytologic diagnosis of AGC (AGC, atypical endocervical cells [AEC], atypical endometrial cells [AEmC]) or a cytologic/histologic diagnosis of AIS documented within the last 6 months who can wait at least one week after the AGC or AIS diagnosis to have an LBC specimen (i.e., ThinPrep) collected and then receive any other intervention; acceptable time frame range is 4 days prior to registration to 7 days after registration

• Patients with positive HPV results who are willing to undergo a complete histologic examination of the uterus and cervix, including the cervical transformation zone, within 6 months of the AGC or AIS diagnosis (histologic examination includes a loop electrosurgical excision procedure [LEEP], loop excision of the transformation zone [LETZ], excisional cone biopsy, or hysterectomy)

• Patients must have signed an approved informed consent and authorization permitting release of personal health information

Exclusion Criteria:

• Patients who have had a hysterectomy

• History of endometrial hyperplasia or cancer of the endometrium, vagina, or cervix

• Patients who have previously been treated, or are currently being treated with radiation therapy or chemotherapy for vaginal or cervical cancer

• Patients who are known to be human immunodeficiency virus (HIV)-positive

• Patients who are pregnant and thought to be at risk for excessive bleeding or preterm labor if a cone biopsy is performed

Related Conditions & MeSH terms

• Atypical Endometrial Hyperplasia
• Endometrial Hyperplasia
• Human Papillomavirus Infection
• Hyperplasia
• Papillomavirus Infections
• Stage 0 Cervical Cancer AJCC v7

Intervention

Other:
• Cytology Specimen Collection Procedure
Correlative studies
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
Japan	Hyogo Cancer Center	Akashi-city	Hyogo
Japan	Hiroshima University Hospital	Hiroshima City
Japan	Kagoshima City Hospital	Kagoshima City	Kagoshima
Japan	Kure National Hospital	Kure	Hiroshima
Japan	Shikoku Cancer Center	Matsuyama
Japan	National Kyushu Cancer Center	Minami-ku
Japan	Jikei University School of Medicine	Minato-ku, Tokyo
Japan	University of the Ryukyus Hospital-Col Health Scnc	Nakagami-gun	Okinawa
Japan	Niigata University Medical and Dental Hospital	Niigata City	Niigata
Japan	Kindai University	Osaka
Japan	Saitama Medical University International Medical Center	Saitama
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Tohoku University School of Medicine	Sendai	Aoba-ku
Japan	Keio University	Shinjuku-ku	Tokyo
Japan	Iwate Medical University Hospital	Shiwa-gun	Iwate
Japan	National Cancer Center Hospital	Tokyo
Japan	Tottori University	Tottori
Korea, Republic of	Keimyung University-Dongsan Medical Center	Dalseo-gu	Daegu
Korea, Republic of	National Cancer Center-Korea	Goyang-si	Gyeonggi-do
Korea, Republic of	Gachon University Gil Hospital	Incheon
Korea, Republic of	Inha University	Jung-gu	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam City	Kyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Catholic University of Korea-Seoul Saint Mary's Hospital	Seoul	Korea
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Kyung Hee University Hospital at Gangdong	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yonsei University Health System-Severance Hospital	Seoul
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon
United States	Woman's Hospital	Baton Rouge	Louisiana
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Big Horn Basin Cancer Center	Cody	Wyoming
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Delaware Radiation Oncology	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Dublin Methodist Hospital	Dublin	Ohio
United States	Elkhart Clinic	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Central Ohio Breast and Endocrine Surgery	Gahanna	Ohio
United States	University of Texas Medical Branch	Galveston	Texas
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Hartford Hospital	Hartford	Connecticut
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Memorial Hermann Texas Medical Center	Houston	Texas
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Providence Medical Center	Kansas City	Kansas
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Joseph Health Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Truman Medical Centers	Kansas City	Missouri
United States	Community Howard Regional Health	Kokomo	Indiana
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	UTMB Cancer Center at Victory Lakes	League City	Texas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Kansas Institute of Medicine Cancer and Blood Center	Lenexa	Kansas
United States	Minimally Invasive Surgery Hospital	Lenexa	Kansas
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	OhioHealth Mansfield Hospital	Mansfield	Ohio
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	OhioHealth Marion General Hospital	Marion	Ohio
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
United States	Community Medical Hospital	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Saint Alphonsus Medical Center-Nampa	Nampa	Idaho
United States	Norris Cotton Cancer Center-Nashua	Nashua	New Hampshire
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Licking Memorial Hospital	Newark	Ohio
United States	Newark Radiation Oncology	Newark	Ohio
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Lakeland Hospital Niles	Niles	Michigan
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	Saint Joseph Hospital - Orange	Orange	California
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina
United States	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana
United States	Maine Medical Center-Bramhall Campus	Portland	Maine
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Saint Joseph Oncology Inc	Saint Joseph	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	Community Medical Center	Scranton	Pennsylvania
United States	Geisinger Medical Oncology-Selinsgrove	Selinsgrove	Pennsylvania
United States	Advent Health - Shawnee Mission Medical Center	Shawnee Mission	Kansas
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Avera Cancer Institute	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	South Bend Clinic	South Bend	Indiana
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Baystate Medical Center	Springfield	Massachusetts
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Olive View-University of California Los Angeles Medical Center	Sylmar	California
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Michiana Hematology Oncology PC-Westville	Westville	Indiana
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
GOG Foundation	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Japan,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biomarker expression, loss of heterozygosity (LOH), chromosome gains, and chromosome losses in tissue from the highest grade or most abnormal lesions in women with AGC	Exploratory analyses of genomic alterations, including LOH as well as chromosome gains and chromosome losses will be performed to identify genomic alterations associated with cervical dysplasia/neoplasia.	Baseline
Other	CA-IX expression, combined p16 and Ki67 expression, and MCM2 expression in LBC specimens	Will be used to see which subset of markers will provide the higher and sensitivity in the diagnosis of cervical AIS.	Baseline
Primary	Biomarker expression in patients from North America	CA-IX, p16, Ki-67, and MCM2 expression in LBC specimens is measured via IHC. A logistic regression and receiver operating characteristic (ROC)-type analysis will be performed.	Baseline
Primary	Biomarker expression in patients from Japan	CA-IX, p16, Ki-67, and MCM2 expression in LBC specimens is measured via IHC. A logistic regression and ROC-type analysis will be performed.	Baseline
Primary	Biomarker expression in patients from Korea	CA-IX, p16, Ki-67, and MCM2 expression in LBC specimens is measured via IHC. A logistic regression and ROC-type analysis will be performed.	Baseline
Secondary	Effect of patient age on the accuracy of diagnosis based on CA-IX, HPV, p16, Ki-67, and/or MCM2 expression in the North American population	Logistic regression analyses will be performed to assess the effect of age and country on sensitivity, specificity, false positive rate (FPR), and complement negative predictive value (NPVC.). For each country and at each age, an upper 95% confidence limit will be calculated for the NPVC.	Baseline
Secondary	Effect of patient age on the accuracy of diagnosis based on CA-IX, HPV, p16, Ki-67, and/or MCM2 expression in the Korean and Japanese populations	Logistic regression analyses will be performed to assess the effect of age and country on sensitivity, specificity, FPR, and NPVC. For each country and at each age, an upper 95% confidence limit will be calculated for the NPVC.	Baseline