Clinical trial NCT05179447: PROfiling Based Endometrial Cancer Adjuvant Therapy
Official title: Randomized Phase III Trial of Molecular Profile-based Versus Standard Recommendations for Adjuvant Therapy for Women With Early Stage Endometrioid Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Endometrial Cancer Stage I
Endometrial Cancer Stage II
Lead sponsor: Women's Hospital School Of Medicine Zhejiang University
Sponsor class: OTHER
Collaborators: name: Tongji Hospital
name: Qilu Hospital of Shandong University
name: Obstetrics & Gynecology Hospital of Fudan University
name: Sun Yat-sen University
name: Peking University People's Hospital
name: Shanghai First Maternity and Infant Hospital
name: Xiangya Hospital of Central South University
name: Anhui Provincial Cancer Hospital
name: Ningbo Women & Children's Hospital
name: Ningbo No. 1 Hospital
First posted: 2022-01-05
Enrollment: 590
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Total recurrence
timeFrame: 3 years
Secondary outcomes:
measure: Relapse-free survival
timeFrame: 3 years, 5 years
measure: Survival
timeFrame: 3 years, 5 years
measure: Adverse events
timeFrame: 3 years, 5 years
measure: Health-related cancer-specific quality of life
timeFrame: 3 years, 5 years
measure: Endometrial cancer related health care costs
timeFrame: 3 years, 5 years
Other outcomes:
measure: Recurrence (vaginal and total) per risk profile
timeFrame: 3 years, 5 years
Locations:
city: Wuhan
country: China
facility: Tongji Hospital, Huazhong University of Science and Technology
state: Hubei
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Hangzhou
country: China
facility: Women's Hospital School of Medicine Zhejiang University
state: Zhejiang
city: Beijing
country: China
facility: Peking University Peoples Hospital
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Hospital
city: Ningbo
country: China
facility: Ningbo First Hospital
city: Ningbo
country: China
facility: Ningbo Women and Children's Hospital
city: Shanghai
country: China
facility: Obstetrics & Gynecology Hospital of Fudan University
city: Shanghai
country: China
facility: Shanghai First Maternity and Infant Hospital
Study officials:
affiliation: Women's Hospital School Of Medicine Zhejiang University
name: Xinyu Wang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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.
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.