Clinical trial NCT00892866: CA-IX, p16, Proliferative Markers, and HPV in Diagnosing Cervical Lesions in Patients With Abnormal Cervical Cells
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Atypical Endometrial Hyperplasia
Human Papillomavirus Infection
Stage 0 Cervical Cancer AJCC v7
Lead sponsor: GOG Foundation
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-05-05
Enrollment: 877
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Biomarker expression in patients from North America
timeFrame: Baseline
measure: Biomarker expression in patients from Japan
timeFrame: Baseline
measure: Biomarker expression in patients from Korea
timeFrame: Baseline
Secondary outcomes:
measure: 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
timeFrame: Baseline
measure: 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
timeFrame: Baseline
Other outcomes:
measure: 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
timeFrame: Baseline
measure: CA-IX expression, combined p16 and Ki67 expression, and MCM2 expression in LBC specimens
timeFrame: Baseline
Locations:
city: Tucson
country: United States
facility: Banner University Medical Center - Tucson
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Cancer Center-North Campus
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA / Jonsson Comprehensive Cancer Center
state: California
city: Orange
country: United States
facility: Saint Joseph Hospital - Orange
state: California
city: Orange
country: United States
facility: UC Irvine Health/Chao Family Comprehensive Cancer Center
state: California
city: Sylmar
country: United States
facility: Olive View-University of California Los Angeles Medical Center
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Britain
country: United States
facility: The Hospital of Central Connecticut
state: Connecticut
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center-Boise
state: Idaho
city: Caldwell
country: United States
facility: Saint Alphonsus Cancer Care Center-Caldwell
state: Idaho
city: Coeur d'Alene
country: United States
facility: Kootenai Health - Coeur d'Alene
state: Idaho
city: Emmett
country: United States
facility: Walter Knox Memorial Hospital
state: Idaho
city: Meridian
country: United States
facility: Idaho Urologic Institute-Meridian
state: Idaho
city: Nampa
country: United States
facility: Saint Alphonsus Medical Center-Nampa
state: Idaho
city: Post Falls
country: United States
facility: Kootenai Clinic Cancer Services - Post Falls
state: Idaho
city: Sandpoint
country: United States
facility: Kootenai Cancer Clinic
state: Idaho
city: Evanston
country: United States
facility: NorthShore University HealthSystem-Evanston Hospital
state: Illinois
city: Mount Vernon
country: United States
facility: Good Samaritan Regional Health Center
state: Illinois
city: Elkhart
country: United States
facility: Elkhart Clinic
state: Indiana
city: Elkhart
country: United States
facility: Michiana Hematology Oncology PC-Elkhart
state: Indiana
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: Kokomo
country: United States
facility: Community Howard Regional Health
state: Indiana
city: La Porte
country: United States
facility: IU Health La Porte Hospital
state: Indiana
city: Mishawaka
country: United States
facility: Michiana Hematology Oncology PC-Mishawaka
state: Indiana
city: Mishawaka
country: United States
facility: Saint Joseph Regional Medical Center-Mishawaka
state: Indiana
city: Plymouth
country: United States
facility: Michiana Hematology Oncology PC-Plymouth
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: South Bend
country: United States
facility: Michiana Hematology Oncology PC-South Bend
state: Indiana
city: South Bend
country: United States
facility: South Bend Clinic
state: Indiana
city: Westville
country: United States
facility: Michiana Hematology Oncology PC-Westville
state: Indiana
city: Kansas City
country: United States
facility: Providence Medical Center
state: Kansas
city: Lenexa
country: United States
facility: Kansas Institute of Medicine Cancer and Blood Center
state: Kansas
city: Lenexa
country: United States
facility: Minimally Invasive Surgery Hospital
state: Kansas
city: Overland Park
country: United States
facility: Menorah Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Saint Luke's South Hospital
state: Kansas
city: Shawnee Mission
country: United States
facility: Advent Health - Shawnee Mission Medical Center
state: Kansas
city: Baton Rouge
country: United States
facility: Woman's Hospital
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Center-Bramhall Campus
state: Maine
city: Scarborough
country: United States
facility: Maine Medical Center- Scarborough Campus
state: Maine
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Niles
country: United States
facility: Lakeland Hospital Niles
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital-Royal Oak
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeland Medical Center Saint Joseph
state: Michigan
city: Saint Joseph
country: United States
facility: Marie Yeager Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Independence
country: United States
facility: Centerpoint Medical Center LLC
state: Missouri
city: Kansas City
country: United States
facility: Truman Medical Centers
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Kansas City
country: United States
facility: Saint Joseph Health Center
state: Missouri
city: Kansas City
country: United States
facility: North Kansas City Hospital
state: Missouri
city: Kansas City
country: United States
facility: Heartland Hematology and Oncology Associates Incorporated
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Lee's Summit
country: United States
facility: Saint Luke's East - Lee's Summit
state: Missouri
city: Liberty
country: United States
facility: Liberty Radiation Oncology Center
state: Missouri
city: Rolla
country: United States
facility: Delbert Day Cancer Institute at PCRMC
state: Missouri
city: Rolla
country: United States
facility: Mercy Clinic-Rolla-Cancer and Hematology
state: Missouri
city: Saint Joseph
country: United States
facility: Heartland Regional Medical Center
state: Missouri
city: Saint Joseph
country: United States
facility: Saint Joseph Oncology Inc
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Springfield
country: United States
facility: CoxHealth South Hospital
state: Missouri
city: Anaconda
country: United States
facility: Community Hospital of Anaconda
state: Montana
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Billings
country: United States
facility: Saint Vincent Healthcare
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Hospital
state: Montana
city: Butte
country: United States
facility: Saint James Community Hospital and Cancer Treatment Center
state: Montana
city: Great Falls
country: United States
facility: Benefis Healthcare- Sletten Cancer Institute
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: Helena
country: United States
facility: Saint Peter's Community Hospital
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Saint Patrick Hospital - Community Hospital
state: Montana
city: Missoula
country: United States
facility: Community Medical Hospital
state: Montana
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Women's Cancer Center of Nevada
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Nashua
country: United States
facility: Norris Cotton Cancer Center-Nashua
state: New Hampshire
city: New Brunswick
country: United States
facility: Saint Peter's University Hospital
state: New Jersey
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center-Einstein Campus
state: New York
city: New York
country: United States
facility: NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Pinehurst
country: United States
facility: FirstHealth of the Carolinas-Moore Regional Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Belpre
country: United States
facility: Strecker Cancer Center-Belpre
state: Ohio
city: Chillicothe
country: United States
facility: Adena Regional Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Center-UC Medical Center
state: Ohio
city: Columbus
country: United States
facility: Mount Carmel East Hospital
state: Ohio
city: Columbus
country: United States
facility: Columbus Oncology and Hematology Associates Inc
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Columbus
country: United States
facility: Grant Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Mark H Zangmeister Center
state: Ohio
city: Columbus
country: United States
facility: Mount Carmel Health Center West
state: Ohio
city: Columbus
country: United States
facility: Doctors Hospital
state: Ohio
city: Delaware
country: United States
facility: Delaware Health Center-Grady Cancer Center
state: Ohio
city: Delaware
country: United States
facility: Delaware Radiation Oncology
state: Ohio
city: Delaware
country: United States
facility: Grady Memorial Hospital
state: Ohio
city: Dublin
country: United States
facility: Dublin Methodist Hospital
state: Ohio
city: Gahanna
country: United States
facility: Central Ohio Breast and Endocrine Surgery
state: Ohio
city: Lancaster
country: United States
facility: Fairfield Medical Center
state: Ohio
city: Mansfield
country: United States
facility: OhioHealth Mansfield Hospital
state: Ohio
city: Marietta
country: United States
facility: Marietta Memorial Hospital
state: Ohio
city: Marion
country: United States
facility: OhioHealth Marion General Hospital
state: Ohio
city: Mount Vernon
country: United States
facility: Knox Community Hospital
state: Ohio
city: Newark
country: United States
facility: Licking Memorial Hospital
state: Ohio
city: Newark
country: United States
facility: Newark Radiation Oncology
state: Ohio
city: Portsmouth
country: United States
facility: Southern Ohio Medical Center
state: Ohio
city: Westerville
country: United States
facility: Saint Ann's Hospital
state: Ohio
city: Zanesville
country: United States
facility: Genesis Healthcare System Cancer Care Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists and Research Institute-Tulsa
state: Oklahoma
city: Baker City
country: United States
facility: Saint Alphonsus Medical Center-Baker City
state: Oregon
city: Ontario
country: United States
facility: Saint Alphonsus Medical Center-Ontario
state: Oregon
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Hazleton
country: United States
facility: Geisinger Medical Center-Cancer Center Hazleton
state: Pennsylvania
city: Lewisburg
country: United States
facility: Geisinger Medical Oncology-Lewisburg
state: Pennsylvania
city: Lewistown
country: United States
facility: Lewistown Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pottsville
country: United States
facility: Geisinger Cancer Services-Pottsville
state: Pennsylvania
city: Scranton
country: United States
facility: Community Medical Center
state: Pennsylvania
city: Selinsgrove
country: United States
facility: Geisinger Medical Oncology-Selinsgrove
state: Pennsylvania
city: State College
country: United States
facility: Geisinger Medical Group
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley/Henry Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Anderson
country: United States
facility: AnMed Health Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: Saint Francis Hospital
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Texas Medical Center
state: Texas
city: League City
country: United States
facility: UTMB Cancer Center at Victory Lakes
state: Texas
city: Cody
country: United States
facility: Big Horn Basin Cancer Center
state: Wyoming
city: Cody
country: United States
facility: Billings Clinic-Cody
state: Wyoming
city: Sheridan
country: United States
facility: Welch Cancer Center
state: Wyoming
city: Sendai
country: Japan
facility: Tohoku University School of Medicine
state: Aoba-ku
city: Kure
country: Japan
facility: Kure National Hospital
state: Hiroshima
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Akashi-city
country: Japan
facility: Hyogo Cancer Center
state: Hyogo
city: Shiwa-gun
country: Japan
facility: Iwate Medical University Hospital
state: Iwate
city: Kagoshima City
country: Japan
facility: Kagoshima City Hospital
state: Kagoshima
city: Niigata City
country: Japan
facility: Niigata University Medical and Dental Hospital
state: Niigata
city: Nakagami-gun
country: Japan
facility: University of the Ryukyus Hospital-Col Health Scnc
state: Okinawa
city: Shinjuku-ku
country: Japan
facility: Keio University
state: Tokyo
city: Hiroshima City
country: Japan
facility: Hiroshima University Hospital
city: Matsuyama
country: Japan
facility: Shikoku Cancer Center
city: Minami-ku
country: Japan
facility: National Kyushu Cancer Center
city: Minato-ku, Tokyo
country: Japan
facility: Jikei University School of Medicine
city: Osaka
country: Japan
facility: Kindai University
city: Saitama
country: Japan
facility: Saitama Medical University International Medical Center
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tottori
country: Japan
facility: Tottori University
city: Dalseo-gu
country: Korea, Republic of
facility: Keimyung University-Dongsan Medical Center
state: Daegu
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center-Korea
state: Gyeonggi-do
city: Jung-gu
country: Korea, Republic of
facility: Inha University
state: Incheon
city: Seoul
country: Korea, Republic of
facility: Catholic University of Korea-Seoul Saint Mary's Hospital
state: Korea
city: Seongnam City
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Kyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System-Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
Study officials:
affiliation: Gynecologic Oncology Group
name: Shu-Yuan liao
role: PRINCIPAL_INVESTIGATOR
References: