PROfiling Based Endometrial Cancer Adjuvant Therapy (PROBEAT)

Women's Hospital School Of Medicine Zhejiang University

Status: Enrolling

Conditions: Endometrial Cancer Stage I; Endometrial Cancer Stage II

Treatments: Radiation: External beam radiotherapy; Other: Observation; Radiation: Vaginal brachytherapy; Combination Product: Chemoradiation therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT05179447

IRB-20210340-R

Details and patient eligibility

About

This is a prospective, multicenter, randomized phase III trial among women with endometrioid adenocarcinoma with high-intermediate and intermediate risk features to investigate the role of integrated genomic-pathologic classification to determine if participants should receive no adjuvant therapy, vaginal brachytherapy, external beam radiotherapy or chemo-radiation therapy based on molecular features as compared to standard radiation therapy.

Full description

Adjuvant therapy for women with endometrial cancer has increasingly been tailored to prognostic factors to prevent overtreatment and select those women for adjuvant treatment who will have a clinically relevant reduction of the risk of relapse by the adjuvant treatment. Risk profiles have traditionally been based on clinicopathological factors such as age, stage, grade, Lymph-Vascular Space Invasion (LVSI) and depth of invasion. Newer, both molecular-genetic (the cancer genome atlas subgroups) have become available which are strongly related to outcomes and risk of cancer spread. Based on 2022 National Comprehensive Cancer Network (NCCN) guideline and the ongoing "Portec-4a" trial, this randomized trial using integrated genomic-pathologic classification to assign adjuvant treatment for women with stage I-II high-intermediate and intermediate risk endometrioid adenocarcinoma.

Enrollment: 590 estimated patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Surgery consisting of a total abdominal or laparoscopic hysterectomy, bilateral salpingectomy, pelvic lymphadenectomy or sentinel lymph node mapping and dissection, with or without para-aortic lymphadenectomy, oophorectomy

2. Histologically confirmed endometrioid type endometrial carcinoma, International Federation of Gynecology and Obstetrics (FIGO) 2009 stage I, with one of the following combinations of stage and grade:

   Stage I A, grade 3 Stage I B, grade 1 or 2 Stage I B, grade 3 Stage II

3. World Health Organization (WHO)-performance status 0-2

4. Written informed consent

Exclusion criteria

1. With residual disease
2. Any other stage and type of endometrial carcinoma
3. Histological types serous carcinoma or clear cell carcinoma (at least 10% if mixed type), or undifferentiated or neuroendocrine carcinoma
4. Uterine sarcoma (including carcinosarcoma)
5. Previous malignancy (except for non-melanomatous skin cancer)
6. Previous pelvic radiotherapy
7. Expected interval between the operation and start of radiotherapy exceeding 8 weeks

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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590 participants in 2 patient groups

Molecular profile based treatment

Experimental group

Description:

Determination of the integrated genomic-pathologic profile to determine adjuvant treatment: observation for POLE-mutated profile; vaginal brachytherapy for intermediate profile; chemo-radiotherapy for p53-abnormal profile.

Treatment:

Combination Product: Chemoradiation therapy

Radiation: Vaginal brachytherapy

Other: Observation

Radiotherapy

Active Comparator group

Description:

Adjuvant vaginal brachytherapy for intermediate risk (stage I A with G3 or stage I B with G1-2) and external beam pelvic radiotherapy for high-intermediate risk (stage I B with G3, or stage II) (standard treatment)

Treatment:

Radiation: Vaginal brachytherapy

Radiation: External beam radiotherapy