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

Phase 3

Not yet recruiting

• Conditions: Adjuvant Radiotherapy; Molecular Classification; Endometrial Cancer
• Interventions: Radiation: Vaginal brachytherapy; Radiation: Pelvic external beam radiotherapy; Other: Observation; Drug: Chemotherapy

• Registration Number: NCT05524389
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

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.

Detailed 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.

Study Timeline

• Status Verified: 2022-08
• Study First Submitted: 2022-08-30
• Study First Submitted QC: 2022-08-31
• Study First Posted: 2022-09-01
• Last Update Submitted: 2022-11-20
• Last Update Posted: 2022-11-23
• Study Start: 2022-12-01
• Primary Completion: 2026-12-01
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 624

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Molecular classification based treatment	Vaginal brachytherapy	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.
Molecular classification based treatment	Pelvic external beam radiotherapy	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.
Molecular classification based treatment	Observation	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.
Molecular classification based treatment	Chemotherapy	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.
Conventional risk stratification based treatment	Pelvic external beam radiotherapy	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)
Conventional risk stratification based treatment	Chemotherapy	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)
Conventional risk stratification based treatment	Vaginal brachytherapy	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)

Primary Outcome Measures

Name	Time	Method
Loco-regional recurrence (LRR)	3-year	Loco-regional recurrence (LRR) is defined as the first recurrence in the vagina or pelvic cavity during follow-up, which was confirmed by imaging examination or biopsy pathology.

Secondary Outcome Measures

Name	Time	Method
Failure free survival(FFS)	3-year,5-year	FFS is defined as the time from randomization to recurrence,distant metastasis or death from any cause,whichever is first.
Overall survical(OS)	3-year,5-year	Overall survival is calculated from randomization to death from any cause.
Cumulative vaginal recurrence	3-year,5-year	Recurrence in the vaginal area during follow-up
De-escalation rate of treatment	3-year	Comparison of the proportion of patients in two groups with the same clinicopathologic factors (FIGO, G, LVSI, age) downgraded from EBRT to VBT or from adjuvant radiotherapy (EBRT or VBT) to observation.
Incidence of Acute and lateToxicities	3-year,5-year	Acute radiation enteritis, radiation cystitis, radiation lymphopenia, late radiation enteritis, radiation cystitis, vaginal stenosis or shortening, lymphedema, bone marrow suppression according to CTCAE v 5.0.
Cumulative pelvic recurrence	3-year,5-year	Recurrence in the pelvic area, including the vagina, during follow-up
Distance metastasis(DM)	3-year,5-year	Distant metastasis (such as bone, lung, liver, brain, non-pelvic regional lymph node metastasis).
Health-related cancer-specific quality of life	3-year,5-year	General quality of life and general cancer related symptoms is accessed by Quality of Life Core Questionnaire (QLQC-30), ,scored as quite a bit/very much vs no or mild symptoms
Endometrial cancer related health care costs	3 years, 5 years	All hospital based health care costs used with primary treatment or during follow-up for treatment of adverse events and/or treatment for relapse.