Study of Early Stage Endometrial Cancer Based on Molecular Classification and Traditional Risk Stratification to Guide Adjuvant Radiotherapy Decisions

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Not yet enrolling; Phase 3

Conditions: Endometrial Cancer; Molecular Classification; Adjuvant Radiotherapy

Treatments: Other: Observation; Drug: Chemotherapy; Radiation: Pelvic external beam radiotherapy; Radiation: Vaginal brachytherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT05524389

ECMC-GART

Details and patient eligibility

About

The purpose of this study is to compare the efficacy and toxicity of early stage endometrial cancer based on molecular classification and conventional risk stratification adjuvant therapy decision-making, and to provide high-quality evidence-based medical evidence for individualized adjuvant therapy selection under the guidance of fine stratification system of endometrial cancer.

Full description

This is an investigator-initiated prospective, national multicentre, phase III, randomised, open, non-inferiority clinical study. The study hypothesis is that adjuvant radiotherapy decision for early-stage endometrial cancer which is based on molecular classification can achieve de-escalation of adjuvant treatment without reducing local tumour control and survival, thereby potentially further reducing radiotherapy-related toxicity and improving quality of life, compared to using conventional risk stratification. The primary endpoint of this study is the 3-year local recurrence rate.

Enrollment: 624 estimated patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Women aged 18-75.

2. Patients with newly histologically confirmed Endometrioid adenocarcinoma.

3. ECOG score 0-2

4. Surgery consisting of a total hysterectomy and bilateral salpingo-oophorectomy, pelvic lymphadenectomy or sentinel lymph node biopsy, with or without para-aortic lymphadenectomy, oophorectomy

5. Patients with FIGO staging(2009 edition) I or II and meet one of the following conditions:

   1. Stage IA G1-2 with massive LVSI+ or age ≥ 60 years
   2. Stage IA G3, regardless of LVSI status
   3. Stage IB G1-3, regardless of LVSI status
   4. Stage II, regardless of tumor grade and LVSI status

6. Patients can understand the study protocol and voluntarily participate in the study, and give written informed consent before treatment.

Exclusion criteria

1. Not FIGO stage I-II.
2. Residual tumor or positive margin.
3. Mixed carcinoma, sarcoma or carcinosarcoma
4. Previous history of malignant tumor
5. Previous history of pelvic radiotherapy
6. The interval between surgery and radiotherapy is more than 12 weeks.
7. With serious medical complications, such as heart disease, lung disease and other diseases that cannot tolerate the whole course of radiotherapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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624 participants in 2 patient groups

Molecular classification based treatment

Experimental group

Description:

Establishment of molecular-clinicopathological classification to make adjuvant treatment decisions: observation for favourable group; vaginal brachytherapy(VBT) for intermediate group; external beam radiotherapy(EBRT) for unfavourable group. Molecular-clinicopathological classification strategy：Favourable group：POLE-mutated. CTNNB1(wide-type)with IA (G1-3) or IB(G1-2)and LVSI(lymph-vascular space invasion) focal/-. Intermediate group：MMRD and LVSI focal/-. CTNNB1(wide-type) and IB(G3) or II with LVSI focal/-. CTNNB1-mutated and IA(G1-3) or IB (G1-2) with LVSI focal/-. Unfavourable group: TP53 mutation. CTNNB1-mutated and IB (G3) or II. Substantial LVSI.

Treatment:

Other: Observation

Radiation: Vaginal brachytherapy

Drug: Chemotherapy

Radiation: Pelvic external beam radiotherapy

Conventional risk stratification based treatment

Active Comparator group

Description:

Adjuvant vaginal brachytherapy alone for intermediate risk patients (IA G1-2 with LVSI present or age\>60, IA G3 or IB G1-2 regardless of LVSI status). EBRT for high-intermediate risk (stage I B with G3, or stage II)

Treatment:

Radiation: Vaginal brachytherapy

Drug: Chemotherapy

Radiation: Pelvic external beam radiotherapy