Biomarkers in Samples From Patients With Endometrial Cancer

NCT01199250 | Withdrawn

• 8 other identifiers: GOG-8020NCI-2011-02868CDR0000684553P50CA134254R01CA071754R21CA133295U10CA027469U10CA037517
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (12)

• Clinical sensitivity and specificity of epigenetic biomarkers in a cohort of blind samples (Project 2)

  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.

  1 month

• Confirmation of CpG island loci frequently hypermethylated in EECs exhibiting recurrence (Project 2)

  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).

  1 month

• Development of a molecular screening regimen to compliment family history risk assessment for the detection of Lynch syndrome (Project 3)

  1 month

• 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)

  1 month

• Frequency of Lynch syndrome-related endometrial cancer and relationships between inherited and acquired DNA mismatch repair defects and clinicopathologic variables (Project 3)

  1 month

• GSK3β inhibition as a therapeutic treatment of endometrial cancer and role of inhibiting other ERK substrates in endometrial cancer cell lines (Project 4)

  1 month

• Identification of cognate FGF ligands and receptors expressed in normal endometrium and endometrial cancers (Project 1)

  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).

  1 month

• Identification of profiles of CpG island hypermethylation for stratifying subtypes of EECs (Project 2)

  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.

  1 month

• 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)

  1 month

• 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)

  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.

  1 month

• Relationship between inherited variation in the MLH1 DNA repair gene and somatic (acquired) inactivation of MLH1 in sporadic endometrial cancer (Project 3)

  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.

  1 month

• Role of FGFR2 mutations in low, intermediate and high risk endometrial cancers (Project 1)

  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.

  1 month

Study Arms (1)

Basic science (biomarker analysis)

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

Other: Laboratory Biomarker Analysis

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Basic science (biomarker analysis)

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with endometrial cancer

You may qualify if:

• Samples available from one of the following:
• GOG-0210
• Washington University School of Medicine Siteman Cancer Center

Sponsors & Collaborators

• Gynecologic Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Gynecologic Oncology Group

Philadelphia, Pennsylvania, 19103, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms, Hereditary Nonpolyposis

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Paul Goodfellow

  Gynecologic Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2010
• First Posted: September 10, 2010
• Study Start: January 1, 2010
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: August 14, 2024

Record last verified: 2024-08

Locations

US (1)