Biomarkers in Samples From Patients With Endometrial Cancer

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2015 by Gynecologic Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Gynecologic Oncology Group
ClinicalTrials.gov Identifier:
NCT01199250
First received: September 9, 2010
Last updated: May 27, 2015
Last verified: May 2015
  Purpose

This research study is studying biomarkers in samples from patients with endometrial cancer. Studying samples from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.


Condition Intervention
Lynch Syndrome
Recurrent Uterine Corpus Carcinoma
Stage I Uterine Corpus Cancer
Stage II Uterine Corpus Cancer
Stage III Uterine Corpus Cancer
Stage IV Uterine Corpus Cancer
Other: Laboratory Biomarker Analysis

Study Type: Observational
Study Design: Time Perspective: Retrospective
Official Title: Specialized Program of Research Excellence (SPORE) in Endometrial Cancer

Resource links provided by NLM:


Further study details as provided by Gynecologic Oncology Group:

Primary Outcome Measures:
  • Clinical sensitivity and specificity of epigenetic biomarkers in a cohort of blind samples (Project 2) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    ROC curves used to describe the discriminatory characteristics of candidate biomarkers. From the competing risk model, the coefficients of the clinicopathological covariates and the hypermethylation levels of each biomarker will indicate the association of these factors with each of the four types of survivals. The significance of association will be indicated by P-values, and hazard rates will also be provided.

  • Confirmation of CpG island loci frequently hypermethylated in EECs exhibiting recurrence (Project 2) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Proportion of methylated samples and 95% confidence interval calculated for each marker, recurrent and non-recurrent samples. Will determine statistical significance of mean difference in DMH methylation levels between methylated and non-methylated samples on basis of two-sided two sample t-tests or nonparametric Wilcoxon tests (if normality is in question). Binary methylation status tabulated with recurrence status to formulate 2 by 2 contingency table. Existence of significant association indicated by a <0.05 p-value from Chi-square test or Fisher test (in case of small counts).

  • Development of a molecular screening regimen to compliment family history risk assessment for the detection of Lynch syndrome (Project 3) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Expression of candidate ERK1/2 substrates in the normal endometrium, primary endometrial cancers and endometrial cancer cell lines dependence of substrate phosphorylation on ERK (Project 4) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Frequency of Lynch syndrome-related endometrial cancer and relationships between inherited and acquired DNA mismatch repair defects and clinicopathologic variables (Project 3) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • GSK3β inhibition as a therapeutic treatment of endometrial cancer and role of inhibiting other ERK substrates in endometrial cancer cell lines (Project 4) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Identification of cognate FGF ligands and receptors expressed in normal endometrium and endometrial cancers (Project 1) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Loss of expression or overexpression for each of FGFs/FGFRs will be described using contingency tables and the overall between-group differences will be compared using Chi-square test or Fisher's exact test as appropriate. For each marker, the nuclear positivity and cytoplasmic positivity will be evaluated separately. Proportional hazards Cox models will be fitted for each FGFR receptor or FGF ligand to evaluate its effect on PFS, ECS, and OS. Multivariate Cox model will be developed while considering biomarkers that have shown trend of significance in univariate analyses (permuted p < 0.2).

  • Identification of profiles of CpG island hypermethylation for stratifying subtypes of EECs (Project 2) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Descriptive statistics including mean, median and standard deviation will be summarized for the recurrent and non-recurrent groups across the 54 samples. Graphical presentation of the data will be provided by use of box-whisker plots and scatter plots.

  • Predictive and prognostic accuracy of a panel of SNPs alone and with informative clinical, surgical, and pathologic variables in a cohort of Caucasian women with stage IB or IC vs IIIC endometrioid endometrial cancer from WUSM and GOG-0210 (Project 5) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Relationship between ERK substrate phosphorylation status and upstream ERK signaling pathway activation in primary endometrial cancers and clinicopathologic significance of ERK substrate expression(Project 4) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    The primary endpoints are protein amounts from quantitative Western blots and IHC-based ordinal scores describing intensity of staining and percentage of cells staining in the nucleus, cytoplasm and a combination of both locations.

  • Relationship between inherited variation in the MLH1 DNA repair gene and somatic (acquired) inactivation of MLH1 in sporadic endometrial cancer (Project 3) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    The primary association analysis for the case-control association study will be 2 x 2 contingency table analysis using chi squared tests. The allele frequency for each SNP will be compared for all cases and controls.

  • Role of FGFR2 mutations in low, intermediate and high risk endometrial cancers (Project 1) [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Clinical outcome in FGFR2 mutation carriers will be compared with survival for women with no mutations. Effect of the mutation over time using survival modeling also considered. OS and PFS described using Cox model. PFI time and ECS time described using competing risks model. Prognostic factors will be evaluated in univariate and multivariate analyses. Variables associated with each primary endpoint (OS, DFS, PHI and ECS) at the 10% level on the basis of univariate models will be introduced in the multivariate models. Significance levels for all analyses will be set at a p-value of 0.05.


Estimated Enrollment: 3600
Study Start Date: January 2100
Estimated Primary Completion Date: January 2100 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Basic science (biomarker analysis)
Previously collected samples are analyzed for biomarker and other laboratory analyses.
Other: Laboratory Biomarker Analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Assess the frequency and spectrum of mutations in fibroblast growth factor receptor 2 (FGFR2) in low-, intermediate-, and/or high-risk endometrioid endometrial cancer from GOG-0210. (Project 1) II. Determine the relationship between FGFR2 mutation and clinicopathologic variables including disease-free and overall survival in low-, intermediate-, and/or high-risk endometrial cancer from GOG-0210. (Project 1) III. Identify the cognate FGF ligands and receptors expressed in normal endometrium and endometrial cancers, and examine their expression on multiple tissue microarrays for GOG-0210 to determine their association with clinical outcome. (Project 1) IV. Identify epigenetic biomarkers (differential methylation of CpG island loci) associated with recurrence and disease progression in endometrioid endometrial cancer from Washington University School of Medicine (WUSM). (Project 2) V. Confirm epigenetic biomarkers (differential methylation of CpG island loci) associated with recurrent and disease progression in endometrioid endometrial cancer from GOG-0210. (Project 2) VI. Define the performance (sensitivity and specificity) of epigenetic biomarkers associated with recurrence and disease progression in endometrioid endometrial cancer from an independent cohort of cases from GOG-0210. (Project 2) VII. Develop a molecular screening regimen to compliment family history risk assessment to identify carriers of Hereditary Non-Polyposis Colorectal Cancer (HNPCC)-related and other forms of inherited endometrial cancer from GOG-0210 that was not ascertained by family history. (Project 3) VIII. Estimate the prevalence of HNPCC-related and other forms of inherited endometrial cancer in GOG-0210. (Project 3) IX. Define the relationship between defective DNA mismatch repair and clinical and epidemiological factors in GOG-0210. (Project 3) X. Determine the clinicopathologic significance of mismatch-repair defects including associations with disease-free and overall survival in GOG-0210. (Project 3) XI. Assess expression of five candidate ERK1/2 substrates in the normal endometrium, primary endometrial cancers (from WUSM and GOG-0210) and endometrial cancer cell lines and determine if substrate phosphorylation is ERK-dependent. (Project 4) XII. Determine the relationship between ERK substrate-phosphorylation status and upstream ERK-signaling pathway activation in primary endometrial cancers from WUSM and GOG-0210. (Project 4 XIII. Determine the clinicopathologic significance of ERK substrate expression in primary endometrial cancers from WUSM and GOG-0210. (Project 4) XIV. Explore GSK3/3 inhibition as a therapeutic treatment of endometrial cancer and assess the role of inhibiting other ERK substrates in endometrial cell lines. (Project 4) XV. Explore the predictive and prognostic accuracy of a panel of single nucleotide polymorphisms alone and with informative clinical, surgical, and pathologic variables in a cohort of Caucasian women with stage IB or IC vs IIIC endometrioid endometrial cancer from WUSM and GOG-0210. (Project 5)

OUTLINE: This is a multicenter study.

Previously collected samples are analyzed for biomarker and other laboratory analyses.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with endometrial cancer

Criteria

Inclusion Criteria:

  • Samples available from one of the following:

    • GOG-0210
    • Washington University School of Medicine Siteman Cancer Center
  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: NCT01199250

Locations
United States, Pennsylvania
Gynecologic Oncology Group Active, not recruiting
Philadelphia, Pennsylvania, United States, 19103
Sponsors and Collaborators
Gynecologic Oncology Group
Investigators
Principal Investigator: Paul Goodfellow Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: Gynecologic Oncology Group
ClinicalTrials.gov Identifier: NCT01199250     History of Changes
Other Study ID Numbers: GOG-8020, NCI-2011-02868, GOG-8020, CDR0000684553, GOG-8020, GOG-8020, P50CA134254, R01CA071754, R21CA133295, U10CA027469, U10CA037517
Study First Received: September 9, 2010
Last Updated: May 27, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Uterine Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Uterine Diseases

ClinicalTrials.gov processed this record on May 29, 2015