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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by Gynecologic Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Gynecologic Oncology Group
ClinicalTrials.gov Identifier:
NCT00892866
First received: May 2, 2009
Last updated: March 19, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention
Atypical Endocervical Glandular Cell of Undetermined Significance
Atypical Endometrial Hyperplasia
Human Papillomavirus Infection
Stage 0 Cervical Cancer
Other: Cytology Specimen Collection Procedure
Other: Laboratory Biomarker Analysis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
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)

Further study details as provided by Gynecologic Oncology Group:

Primary Outcome Measures:
  • Biomarker expression in patients from North America [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Biomarker expression in patients from Japan [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Biomarker expression in patients from Korea [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • 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 [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • CA-IX expression, combined p16 and Ki67 expression, and MCM2 expression in LBC specimens [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Will be used to see which subset of markers will provide the higher and sensitivity in the diagnosis of cervical AIS.


Estimated Enrollment: 877
Study Start Date: February 2009
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Ancillary-Correlative (biomarkers in cervical cancer)
Patients undergo liquid-based cytology specimen sample collection for analysis of CA-IX, p16, Ki-67, and MCM2 expression via IHC and for the presence of high risk HPV DNA and HPV genotyping.
Other: Cytology Specimen Collection Procedure
Correlative studies
Other Name: Cytologic Sampling
Other: Laboratory Biomarker Analysis
Correlative studies

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

•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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00892866

  Show 107 Study Locations
Sponsors and Collaborators
Gynecologic Oncology Group
Investigators
Principal Investigator: Shu-Yuan Liao Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: Gynecologic Oncology Group
ClinicalTrials.gov Identifier: NCT00892866     History of Changes
Other Study ID Numbers: GOG-0237, NCI-2009-01103, CDR0000632236, GOG-0237, GOG-0237, GOG-0237, U10CA101165, UG1CA189867, N01CM62201
Study First Received: May 2, 2009
Last Updated: March 19, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Endometrial Hyperplasia
Papillomavirus Infections
DNA Virus Infections
Genital Diseases, Female
Tumor Virus Infections
Uterine Diseases
Virus Diseases

ClinicalTrials.gov processed this record on March 25, 2015