PROfiling Based Endometrial Cancer Adjuvant Therapy

Endometrial Cancer Stage I Clinical Trial

— PROBEAT  

Official title:

Randomized Phase III Trial of Molecular Profile-based Versus Standard Recommendations for Adjuvant Therapy for Women With Early Stage Endometrioid Adenocarcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05179447
• Other study ID #: IRB-20210340-R
• Status: Recruiting
• Phase: N/A
• Start date: January 24, 2022
• Est. completion date: January 1, 2027

Study information

• Verified date: December 2023
• Source: Women's Hospital School Of Medicine Zhejiang University
• Contact: Xinyu Wang, MD
• Phone: +86-571-87061501
• Email: wangxinyu[@]zju.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 590
• Est. completion date: January 1, 2027
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Endometrial Cancer Stage I
• Endometrial Cancer Stage II
• Endometrial Neoplasms

Intervention

Radiation:
• Vaginal brachytherapy
Internal radiation of the vaginal vault using a vaginal cylinder. For brachytherapy administered alone it is recommended: suggested dose is either 3 fractions of 7 Gy or 5 fractions of 6 Gy. For brachytherapy administered after completion of External beam radiotherapy (EBRT): Total dose should aim to be 65 Gy, and suggested dose is 2-3 fractions of 5-6 Gy
• External beam radiotherapy
External beam pelvic radiotherapy on a linear accelerator, 45-50 Gy in 25-28 out-patients sessions

Other:
• Observation
No adjuvant therapy, but active follow-up and quality of life questionnaires as in the groups who have adjuvant treatment

Combination Product:
• Chemoradiation therapy
4 adjuvant cycles carboplatin and paclitaxel followed by External beam pelvic radiotherapy (45-50 Gy )

Locations

Country	Name	City	State
China	Peking University Peoples Hospital	Beijing
China	Xiangya Hospital of Central South University	Changsha
China	Sun Yat-Sen University Cancer Hospital	Guangzhou
China	Women's Hospital School of Medicine Zhejiang University	Hangzhou	Zhejiang
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Ningbo First Hospital	Ningbo
China	Ningbo Women and Children's Hospital	Ningbo
China	Obstetrics & Gynecology Hospital of Fudan University	Shanghai
China	Shanghai First Maternity and Infant Hospital	Shanghai
China	Tongji Hospital, Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (11)

Lead Sponsor	Collaborator
Women's Hospital School Of Medicine Zhejiang University	Anhui Provincial Cancer Hospital, Ningbo No. 1 Hospital, Ningbo Women & Children's Hospital, Obstetrics & Gynecology Hospital of Fudan University, Peking University People's Hospital, Qilu Hospital of Shandong University, Shanghai First Maternity and Infant Hospital, Sun Yat-sen University, Tongji Hospital, Xiangya Hospital of Central South University

Country where clinical trial is conducted

China, 

References & Publications (5)

Concin N, Matias-Guiu X, Vergote I, Cibula D, Mirza MR, Marnitz S, Ledermann J, Bosse T, Chargari C, Fagotti A, Fotopoulou C, Gonzalez Martin A, Lax S, Lorusso D, Marth C, Morice P, Nout RA, O'Donnell D, Querleu D, Raspollini MR, Sehouli J, Sturdza A, Taylor A, Westermann A, Wimberger P, Colombo N, Planchamp F, Creutzberg CL. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer. 2021 Jan;31(1):12-39. doi: 10.1136/ijgc-2020-002230. Epub 2020 Dec 18. — View Citation

de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, Colombo A, Fyles A, Baron MH, Jurgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Carinelli S, Provencher D, Hanzen C, Lutgens LCHW, Smit VTHBM, Singh N, Do V, D'Amico R, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC study group. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Mar;19(3):295-309. doi: 10.1016/S1470-2045(18)30079-2. Epub 2018 Feb 12. Erratum In: Lancet Oncol. 2018 Apr;19(4):e184. — View Citation

Leon-Castillo A, Britton H, McConechy MK, McAlpine JN, Nout R, Kommoss S, Brucker SY, Carlson JW, Epstein E, Rau TT, Bosse T, Church DN, Gilks CB. Interpretation of somatic POLE mutations in endometrial carcinoma. J Pathol. 2020 Mar;250(3):323-335. doi: 10.1002/path.5372. Epub 2020 Jan 29. — View Citation

Leon-Castillo A, de Boer SM, Powell ME, Mileshkin LR, Mackay HJ, Leary A, Nijman HW, Singh N, Pollock PM, Bessette P, Fyles A, Haie-Meder C, Smit VTHBM, Edmondson RJ, Putter H, Kitchener HC, Crosbie EJ, de Bruyn M, Nout RA, Horeweg N, Creutzberg CL, Bosse T; TransPORTEC consortium. Molecular Classification of the PORTEC-3 Trial for High-Risk Endometrial Cancer: Impact on Prognosis and Benefit From Adjuvant Therapy. J Clin Oncol. 2020 Oct 10;38(29):3388-3397. doi: 10.1200/JCO.20.00549. Epub 2020 Aug 4. — View Citation

Wortman BG, Bosse T, Nout RA, Lutgens LCHW, van der Steen-Banasik EM, Westerveld H, van den Berg H, Slot A, De Winter KAJ, Verhoeven-Adema KW, Smit VTHBM, Creutzberg CL; PORTEC Study Group. Molecular-integrated risk profile to determine adjuvant radiotherapy in endometrial cancer: Evaluation of the pilot phase of the PORTEC-4a trial. Gynecol Oncol. 2018 Oct;151(1):69-75. doi: 10.1016/j.ygyno.2018.07.020. Epub 2018 Aug 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Recurrence (vaginal and total) per risk profile	Vaginal, pelvic and distant relapse split by risk profile and compared between the 2 arms	3 years, 5 years
Primary	Total recurrence	Vaginal, pelvic or distant recurrence as first failure	3 years
Secondary	Relapse-free survival	Relapse-free survival (survival without relapse)	3 years, 5 years
Secondary	Survival	Overall survival (all-cause death)	3 years, 5 years
Secondary	Adverse events	Treatment-related symptoms according to CTCAE v 5.0	3 years, 5 years
Secondary	Health-related cancer-specific quality of life	Quality of Life Core Questionnaire (QLQC-30) - clinically relevant changes on Quality of Life Core Questionnaire-30 functioning scales, general quality of life and general cancer symptoms, quite a bit/very much vs no or mild symptoms	3 years, 5 years
Secondary	Endometrial cancer related health care costs	All hospital based health care costs used with primary treatment or during followup for treatment of adverse events and/or treatment for relapse	3 years, 5 years