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

A Prospective Multicentre Phase III Randomised Open Clinical Study of Early Stage Endometrial Cancer Based on Molecular Classification and Traditional Risk Stratification to Guide Adjuvant Radiotherapy Decisions

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Endometrial Cancer; Adjuvant Radiotherapy; Molecular Classification
• Intervention / Treatment: Radiation: Vaginal brachytherapy; Radiation: Pelvic external beam radiotherapy; Other: Observation; Drug: Chemotherapy

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 Type: Interventional
• Enrollment (Anticipated): 624
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xiaorong Hou, PhD; Phone Number: +86-13811963013; Email: hxr_pumch@163.com
• Study Contact Backup: Name: Xiaorong Hou, PhD; Phone Number: +86-01069155487; Email: hxr_pumch@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Molecular classification based treatment; 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.	Radiation: Vaginal brachytherapy; High-dose rate vaginal brachytherapy (VBT) was delivered with a vaginal cylinder.For VBT administered alone, the dose is recommended: 3 fractions of 7 Gy or 5 fractions of 6 Gy or 6 fractions of 5 Gy. For VBT administered after completion of EBRT: 2-3 fractions of 4-6 Gy.; Other Names: VBT; Radiation: Pelvic external beam radiotherapy; EBRT was delivered to the pelvic area using a total dose of 45-50.4Gy in 25-28 fractions over 5-6 weeks with the intensity-modulated radiotherapy (IMRT) technique, three-dimensional conformal radiotherapy (3D-CRT) modality; Other Names: Pelvic EBRT; Other: Observation; No radiotherapy is administrated, but active follow-up and quality of life questionnaires is needed after surgery.; Drug: Chemotherapy; Intravenous concurrent or sequential adjuvant chemotherapy consists of carboplatin/paclitaxel, cisplatin/doxorubicin or cisplatin/doxorubicin/paclitaxel, etc.
Active Comparator: Conventional risk stratification based treatment; 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)	Radiation: Vaginal brachytherapy; High-dose rate vaginal brachytherapy (VBT) was delivered with a vaginal cylinder.For VBT administered alone, the dose is recommended: 3 fractions of 7 Gy or 5 fractions of 6 Gy or 6 fractions of 5 Gy. For VBT administered after completion of EBRT: 2-3 fractions of 4-6 Gy.; Other Names: VBT; Radiation: Pelvic external beam radiotherapy; EBRT was delivered to the pelvic area using a total dose of 45-50.4Gy in 25-28 fractions over 5-6 weeks with the intensity-modulated radiotherapy (IMRT) technique, three-dimensional conformal radiotherapy (3D-CRT) modality; Other Names: Pelvic EBRT; Drug: Chemotherapy; Intravenous concurrent or sequential adjuvant chemotherapy consists of carboplatin/paclitaxel, cisplatin/doxorubicin or cisplatin/doxorubicin/paclitaxel, etc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Loco-regional recurrence (LRR)	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.	3-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure free survival(FFS)	FFS is defined as the time from randomization to recurrence,distant metastasis or death from any cause,whichever is first.	3-year,5-year
Overall survical(OS)	Overall survival is calculated from randomization to death from any cause.	3-year,5-year
Cumulative vaginal recurrence	Recurrence in the vaginal area during follow-up	3-year,5-year
Cumulative pelvic recurrence	Recurrence in the pelvic area, including the vagina, during follow-up	3-year,5-year
Distance metastasis(DM)	Distant metastasis (such as bone, lung, liver, brain, non-pelvic regional lymph node metastasis).	3-year,5-year
De-escalation rate of treatment	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.	3-year
Health-related cancer-specific quality of life	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	3-year,5-year
Incidence of Acute and lateToxicities	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.	3-year,5-year
Endometrial cancer related health care costs	All hospital based health care costs used with primary treatment or during follow-up for treatment of adverse events and/or treatment for relapse.	3 years, 5 years

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Peking University First Hospital; Xiangya Hospital of Central South University; Cancer Institute and Hospital, Chinese Academy of Medical Sciences; First Affiliated Hospital Xi'an Jiaotong University; The Affiliated Hospital of Inner Mongolia Medical University; Third Affiliated Hospital of Xinjiang Medical University; The Second Affiliated Hospital of Dalian Medical University; Xijing Hospital, Air Force Medical University of PLA; The 940th Hospital of Joint Logistics Support Force，PLA.; The second hospital Affiliated by Jilin University

Publications and helpful links

General Publications

• Ren K, Wang W, Sun S, Hou X, Hu K, Zhang F. Recurrent patterns after postoperative radiotherapy for early stage endometrial cancer: A competing risk analysis model. Cancer Med. 2022 Jan;11(1):257-267. doi: 10.1002/cam4.4423. Epub 2021 Nov 15.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2022
• Primary Completion (Anticipated): December 1, 2026
• Study Completion (Anticipated): June 30, 2027

Study Registration Dates

• First Submitted: August 30, 2022
• First Submitted That Met QC Criteria: August 31, 2022
• First Posted (Actual): September 1, 2022

Study Record Updates

• Last Update Posted (Actual): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 20, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Endometrial Cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms
• Other Study ID Numbers: ECMC-GART

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No