PErsonalized TReatment for Endometrial Carcinoma

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare the efficacy of adjuvant therapies in women with stage I-II molecular integrated high-intermediate or high-risk endometrial carcinoma. Specifically, the invesigators want to compare: Chemotherapy vs. chemoradiotherapy in p53 abn subtype and nonendometrioid carcinomas. Vaginal brachytherapy vs. whole pelvic radiotherapy in the MMR-D molecular subgroup. Vaginal brachytherapy vs. whole pelvic radiotherapy in the NSMP molecular subgroup.

Detailed Description
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Endometrial carcinomas can be classified into four molecular subgroups, i.e. mismatch repair deficient (MMR-D), p53 abnormal (p53 abn), polymerase-ϵ (POLE) ultramutated, and no specific molecular profile (NSMP). Molecular subgroups can be considered to be distinct diseases as they are associated with different clinicopathologic characteristics, prognoses and, possibly, responses to adjuvant therapy. Molecular classification of endometrial carcinoma is recommended to be implemented in routine clinical practice to improve prognostication and triage to adjuvant therapy. The PErsonalized TReatment for Endometrial Carcinoma (PETREC) trial, led by the Finnish Gynecologic Oncology Group (FINGOG), is a multicenter prospective clinical trial for women with stage I-II molecular integrated high-intermediate or high-risk endometrial carcinoma. The efficacy of chemotherapy vs. chemoradiotherapy is compared in p53 abn subtype and nonendometrioid carcinomas, and vaginal brachytherapy vs. whole pelvic radiotherapy in MMR-D and NSMP molecular subgroups. Patients who consent to follow-up within the trial but not to randomization are treated as recommended in multidisciplinary meetings and enrolled for follow-up only (comprehensive cohort study design). The primary outcome is the 5-year cumulative incidence of disease recurrence. Secondary outcomes are vaginal, pelvic, and distant recurrence rates, 5-year recurrence-free and overall survival, adverse events, and patient-reported symptoms and quality of life. The findings of the trial may eventually help decrease under- and overtreatment and, consequently, improve patient outcome and decrease treatment-associated adverse effects.

Official Title
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PErsonalized TReatment for Endometrial Carcinoma

Conditions
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Endometrial Adenocarcinoma

Intervention / Treatment
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* Other: Comparison of adjuvant therapies
* Other: Comparison of adjuvant therapies


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 100 years WHO performance status 0 to 2 Stage I-II molecular integrated high-intermediate or high-risk endometrial carcinoma Exclusion Criteria: Age <18 years or >100 years WHO performance status >2 Uterine sarcoma A history of malignancy within 5 years Previous pelvic radiotherapy An interval of >30 days between surgery and start of chemotherapy or >8 weeks between surgery and start of radiotherapy (longer intervals may be permitted with investigator´s approval)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Comprehensive cohort design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: p53 abn subtype and nonendometrioid carcinomas<br>p53 abn stage I-II MI (myometrial invasion) >0%; MMR-D/NSMP nonendometrioid stage I-II MI >0% | Other: Comparison of adjuvant therapies<br>* Chemotherapy (paclitaxel-carboplatin) vs. chemoradiotherapy (paclitaxel-carboplatin followed by whole pelvic radiotherapy) Patients assigned to chemotherapy receive paclitaxel (175 mg/m2) and carboplatin (area under curve, 5) every 3 weeks for 6 cycles. The pelvic radiotherapy dose is 45 to 50.4 Gy over 5 to 6 weeks (1.8 Gy per day for 25 to 28 fractions).<br>|
| Experimental: MMR-D molecular subgroup<br>MMR-D stage IA-B grade 1-2, substantial LVSI; MMR-D stage IA grade 3, substantial LVSI; MMR-D stage IB grade 3; MMR-D stage II grade 1-3; | Other: Comparison of adjuvant therapies<br>* Vaginal brachytherapy vs. whole pelvic radiotherapy Patients randomized to vaginal brachytherapy receive cuff brachytherapy at 21 Gy in 3 fractions of 7 Gy at 0.5 cm depth. The pelvic radiotherapy dose is 45 to 50.4 Gy over 5 to 6 weeks (1.8 Gy per day for 25 to 28 fractions).<br>|
| Experimental: NSMP molecular subgroup<br>NSMP stage IA-B grade 1-2, substantial LVSI; NSMP stage IA grade 3, substantial LVSI; NSMP stage IB grade 3; NSMP stage II grade 1-3; | Other: Comparison of adjuvant therapies<br>* Vaginal brachytherapy vs. whole pelvic radiotherapy Patients randomized to vaginal brachytherapy receive cuff brachytherapy at 21 Gy in 3 fractions of 7 Gy at 0.5 cm depth. The pelvic radiotherapy dose is 45 to 50.4 Gy over 5 to 6 weeks (1.8 Gy per day for 25 to 28 fractions).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cancer reappearance | Cumulative incidence of disease recurrence | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Location of cancer reappearance | Vaginal, pelvic, and distant recurrence rates | 5 years | 
| Overall survival | The time from surgery to death | 5 years | 
| Recurrence-free survival | The time from surgery to cancer recurrence | 5 years | 
| Adverse events | Adjuvant therapy-related adverse events | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endometrial carcinoma, Molecular classification, Adjuvant therapy