Clinical trial NCT01199250: Biomarkers in Samples From Patients With Endometrial Cancer
Official title: Specialized Program of Research Excellence (SPORE) in Endometrial Cancer
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
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
Lead sponsor: GOG Foundation
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2010-09-10
Enrollment: 0
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with endometrial cancer

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.

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 criteria: Inclusion Criteria:

* Samples available from one of the following:

  * GOG-0210
  * Washington University School of Medicine Siteman Cancer Center

Primary outcomes:
measure: Clinical sensitivity and specificity of epigenetic biomarkers in a cohort of blind samples (Project 2)
timeFrame: 1 month
measure: Confirmation of CpG island loci frequently hypermethylated in EECs exhibiting recurrence (Project 2)
timeFrame: 1 month
measure: Development of a molecular screening regimen to compliment family history risk assessment for the detection of Lynch syndrome (Project 3)
timeFrame: 1 month
measure: 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)
timeFrame: 1 month
measure: Frequency of Lynch syndrome-related endometrial cancer and relationships between inherited and acquired DNA mismatch repair defects and clinicopathologic variables (Project 3)
timeFrame: 1 month
measure: GSK3β inhibition as a therapeutic treatment of endometrial cancer and role of inhibiting other ERK substrates in endometrial cancer cell lines (Project 4)
timeFrame: 1 month
measure: Identification of cognate FGF ligands and receptors expressed in normal endometrium and endometrial cancers (Project 1)
timeFrame: 1 month
measure: Identification of profiles of CpG island hypermethylation for stratifying subtypes of EECs (Project 2)
timeFrame: 1 month
measure: 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)
timeFrame: 1 month
measure: 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)
timeFrame: 1 month
measure: Relationship between inherited variation in the MLH1 DNA repair gene and somatic (acquired) inactivation of MLH1 in sporadic endometrial cancer (Project 3)
timeFrame: 1 month
measure: Role of FGFR2 mutations in low, intermediate and high risk endometrial cancers (Project 1)
timeFrame: 1 month
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Gynecologic Oncology Group
state: Pennsylvania
Study officials:
affiliation: Gynecologic Oncology Group
name: Paul Goodfellow
role: PRINCIPAL_INVESTIGATOR
References: