Prediction of Recurrence Among Low Risk Endometrial Cancer Patients

Recruiting

• Conditions: FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma; FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma
• Interventions: Procedure: Bilateral Salpingectomy with Oophorectomy; Procedure: Biospecimen Collection; Procedure: Hysterectomy; Other: Laboratory Biomarker Analysis; Procedure: Lymph Node Mapping; Procedure: Sentinel Lymph Node Biopsy

• Registration Number: NCT04604613
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

This study investigates whether molecular testing can help to predict the risk of endometrial cancer coming back (recurrence) after treatment in patients diagnosed with low risk endometrial cancer and scheduled to have surgery to remove the uterus and/or cervix (hysterectomy). Having sentinel lymph node mapping performed may help researchers to see if the cancer has spread in patients with low risk endometrial cancer.

Detailed Description

PRIMARY OBJECTIVE:

I. Validate the use of a molecular panel of estrogen-induced genes to predict recurrence in low risk endometrial cancer.

SECONDARY OBJECTIVES:

I. Calculate the positive predictive value (PPV)/negative predictive value (NPV)/sensitivity (Sens)/specificity (Spec) of lymph node mapping to predict pelvic lymph node involvement.

II. Correlate CA125 and HE4 levels with recurrence and to explore the use of other serum biomarkers to predict recurrence.

III. Describe patterns of recurrence in a low risk patient population. IV. Determine if molecular panel can predict lymph node involvement in low risk endometrial cancer patients who undergo pelvic and para-aortic lymphadenectomy.

V. Compare performance of molecular panel to the Mayo low risk criteria for prediction of lymph node involvement.

VI. Compare performance of molecular panel to the high intermediate risk criteria from Gynecologic Oncology Group, trial 99 (GOG 99) for prediction of recurrence.

VII. Determine the feasibility of lymph node mapping in this patient population.

VIII. Determine the morbidity and mortality of lymph node dissection and mapping.

OUTLINE:

Patients undergo hysterectomy and sentinel lymph node mapping. Patients may also undergo bilateral salpingo-oophorectomy at the direction of the treating physician. If peritoneal disease or other contraindications to lymphatic mapping are detected at the time of surgery, mapping and sentinel node biopsy are performed at the surgeon's discretion. At the time of hysterectomy, patients undergo collection of tissue for molecular testing. Before and after surgery, patients also undergo collection of blood samples for tumor marker analysis.

Study Timeline

• Study Start: 2012-11-08
• Study First Submitted: 2020-10-21
• Study First Submitted QC: 2020-10-21
• Study First Posted: 2020-10-27
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-27
• Last Update Posted: 2024-08-28
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 500

Inclusion Criteria

• Histologically confirmed low grade (grade 1-2) endometrioid type adenocarcinoma
• Candidate for surgery
• No evidence of deep invasion or peritoneal disease in patients that have undergone preoperative imaging
• Patients may have had prior hormonal treatment for the treatment of early endometrial neoplasia. Patients may not have had prior radiation or chemotherapy for treatment of endometrial cancer
• Patients must have a negative pregnancy if of childbearing potential

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Exclusion Criteria

• Histologically confirmed high grade endometrioid or non-endometrioid type endometrial cancer (including serous, clear cell, carcinosarcoma or any mixed tumor containing these cell types)
• Medical co-morbidities making surgery unsafe, as determined by the primary treating physician
• Evidence of deep myometrial invasion, cervical involvement or peritoneal disease on preoperative imaging
• Prior treatment with radiation or chemotherapy for endometrial cancer
• Any contraindication to lymph node mapping

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Ancillary-Correlative (biospecimen collection, node mapping)	Bilateral Salpingectomy with Oophorectomy	Patients undergo hysterectomy and sentinel lymph node mapping. Patients may also undergo bilateral salpingo-oophorectomy at the direction of the treating physician. If peritoneal disease or other contraindications to lymphatic mapping are detected at the time of surgery, mapping and sentinel node biopsy are performed at the surgeon's discretion. At the time of hysterectomy, patients undergo collection of tissue for molecular testing. Before and after surgery, patients also undergo collection of blood samples for tumor marker analysis.
Ancillary-Correlative (biospecimen collection, node mapping)	Lymph Node Mapping	Patients undergo hysterectomy and sentinel lymph node mapping. Patients may also undergo bilateral salpingo-oophorectomy at the direction of the treating physician. If peritoneal disease or other contraindications to lymphatic mapping are detected at the time of surgery, mapping and sentinel node biopsy are performed at the surgeon's discretion. At the time of hysterectomy, patients undergo collection of tissue for molecular testing. Before and after surgery, patients also undergo collection of blood samples for tumor marker analysis.
Ancillary-Correlative (biospecimen collection, node mapping)	Sentinel Lymph Node Biopsy	Patients undergo hysterectomy and sentinel lymph node mapping. Patients may also undergo bilateral salpingo-oophorectomy at the direction of the treating physician. If peritoneal disease or other contraindications to lymphatic mapping are detected at the time of surgery, mapping and sentinel node biopsy are performed at the surgeon's discretion. At the time of hysterectomy, patients undergo collection of tissue for molecular testing. Before and after surgery, patients also undergo collection of blood samples for tumor marker analysis.
Ancillary-Correlative (biospecimen collection, node mapping)	Hysterectomy	Patients undergo hysterectomy and sentinel lymph node mapping. Patients may also undergo bilateral salpingo-oophorectomy at the direction of the treating physician. If peritoneal disease or other contraindications to lymphatic mapping are detected at the time of surgery, mapping and sentinel node biopsy are performed at the surgeon's discretion. At the time of hysterectomy, patients undergo collection of tissue for molecular testing. Before and after surgery, patients also undergo collection of blood samples for tumor marker analysis.
Ancillary-Correlative (biospecimen collection, node mapping)	Biospecimen Collection	Patients undergo hysterectomy and sentinel lymph node mapping. Patients may also undergo bilateral salpingo-oophorectomy at the direction of the treating physician. If peritoneal disease or other contraindications to lymphatic mapping are detected at the time of surgery, mapping and sentinel node biopsy are performed at the surgeon's discretion. At the time of hysterectomy, patients undergo collection of tissue for molecular testing. Before and after surgery, patients also undergo collection of blood samples for tumor marker analysis.
Ancillary-Correlative (biospecimen collection, node mapping)	Laboratory Biomarker Analysis	Patients undergo hysterectomy and sentinel lymph node mapping. Patients may also undergo bilateral salpingo-oophorectomy at the direction of the treating physician. If peritoneal disease or other contraindications to lymphatic mapping are detected at the time of surgery, mapping and sentinel node biopsy are performed at the surgeon's discretion. At the time of hysterectomy, patients undergo collection of tissue for molecular testing. Before and after surgery, patients also undergo collection of blood samples for tumor marker analysis.

Primary Outcome Measures

Name	Time	Method
2-year recurrence	At 2 years	Will validate a model's ability to predict 2-year recurrence in low-risk endometrial cancer patients.

Secondary Outcome Measures

Name	Time	Method
Morbidity and mortality prevalence associated with lymph node dissection	Up to 2 years	Morbidity and mortality prevalence associated with lymph node dissection and mapping will be calculated with 95% confidence intervals.
Predictive ability of marker panel in recurrence	Up to 2 years	Will examine how well the predictive ability of the marker panel agrees with the predictive ability of the high intermediate risk criteria from Gynecologic Oncology Group, trial 99 using this patient population. 95% confidence intervals will be calculated for all concordance statistics.
Predictive ability of lymph node mapping in pelvic lymph node involvement	Up to 2 years	Will calculate the sensitivity (true positive fraction \[TPF\]), specificity (1-false positive fraction \[FPF\]), positive predictive value (PPV), and negative predictive value (NPV) of lymph node mapping in predicting pelvic lymph node involvement, along with 2-sided 95% confidence intervals.
Patterns of recurrence	Up to 2 years	Will determine which demographic and clinical traits are most associated with recurrence rate using proportional hazards models and with 2-year recurrence using logistic regression models. Will conduct univariate analyses using log-rank tests and Fisher's exact tests, in the case of categorical traits, and proportional hazards and logistic regression models, in the case of continuous traits. Will examine all traits for violations of the proportional hazards assumption (recurrence rate models), and will examine all continuous traits for functional form (recurrence and recurrence rate models). Will use the same methods to determine whether CA125 and HE4 is associated with recurrence and recurrence rate.
Feasibility of lymph node mapping	Up to 2 years	Feasibility of lymph node mapping in this patient population will be determined after examining the TPF, FPF, PPV, and NPV.
Predictive ability of molecular panel in lymph node involvement	Up to 2 years	Will use Cartesian and Regression Tree Analysis and logistic regression to determine if the molecular panel can predict lymph node involvement. Will assess the use of the model by calculating sensitivity, specificity, PPV, and NPV. Additionally, will examine how often the results of the molecular panel model concur with the Mayo low risk criteria for prediction of lymph node involvement. All agreement statistics will be presented with their 95% confidence intervals.

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States