PROfiling Based Endometrial Cancer Adjuvant Therapy

NCT05179447 | Recruiting

• 1 other identifier: IRB-20210340-R
• Study Type: interventional
• Target: 590
• Locations: 1 country
• Sites: 10

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.

Conditions

Endometrial Cancer Stage I; Endometrial Cancer Stage II

Outcome Measures

Primary Outcomes (1)

• Total recurrence

  Vaginal, pelvic or distant recurrence as first failure

  3 years

Secondary Outcomes (5)

• Relapse-free survival

  3 years, 5 years

• Survival

  3 years, 5 years

• Adverse events

  3 years, 5 years

• Health-related cancer-specific quality of life

  3 years, 5 years

• Endometrial cancer related health care costs

  3 years, 5 years

Other Outcomes (1)

• Recurrence (vaginal and total) per risk profile

  3 years, 5 years

Study Arms (2)

Molecular profile based treatment

EXPERIMENTAL

Determination of the integrated genomic-pathologic profile to determine adjuvant treatment: observation for POLE-mutated profile; vaginal brachytherapy for intermediate profile; chemo-radiotherapy for p53-abnormal profile.

Radiation: Vaginal brachytherapy; Other: Observation; Combination Product: Chemoradiation therapy

Radiotherapy

ACTIVE COMPARATOR

Adjuvant vaginal brachytherapy for intermediate risk (stage I A with G3 or stage I B with G1-2) and external beam pelvic radiotherapy for high-intermediate risk (stage I B with G3, or stage II) (standard treatment)

Radiation: Vaginal brachytherapy; Radiation: External beam radiotherapy

Interventions

Vaginal brachytherapy RADIATION

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

Molecular profile based treatment; Radiotherapy

External beam radiotherapy RADIATION

External beam pelvic radiotherapy on a linear accelerator, 45-50 Gy in 25-28 out-patients sessions

Radiotherapy

Observation OTHER

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

Molecular profile based treatment

Chemoradiation therapy COMBINATION_PRODUCT

4 adjuvant cycles carboplatin and paclitaxel followed by External beam pelvic radiotherapy (45-50 Gy )

Molecular profile based treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• World Health Organization (WHO)-performance status 0-2
• Written informed consent

You may not qualify if:

• With residual disease
• Any other stage and type of endometrial carcinoma
• Histological types serous carcinoma or clear cell carcinoma (at least 10% if mixed type), or undifferentiated or neuroendocrine carcinoma
• Uterine sarcoma (including carcinosarcoma)
• Previous malignancy (except for non-melanomatous skin cancer)
• Previous pelvic radiotherapy
• Expected interval between the operation and start of radiotherapy exceeding 8 weeks

Sponsors & Collaborators

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

Study Sites (10)

Tongji Hospital, Huazhong University of Science and Technology

Wuhan, Hubei, China

RECRUITING

Qilu Hospital of Shandong University

Jinan, Shandong, China

RECRUITING

Women's Hospital School of Medicine Zhejiang University

Hangzhou, Zhejiang, 310000, China

RECRUITING

Peking University Peoples Hospital

Beijing, China

NOT YET RECRUITING

Xiangya Hospital of Central South University

Changsha, China

RECRUITING

Sun Yat-Sen University Cancer Hospital

Guangzhou, China

NOT YET RECRUITING

Ningbo First Hospital

Ningbo, China

RECRUITING

Ningbo Women and Children's Hospital

Ningbo, China

RECRUITING

Obstetrics & Gynecology Hospital of Fudan University

Shanghai, China

NOT YET RECRUITING

Shanghai First Maternity and Infant Hospital

Shanghai, China

NOT YET RECRUITING

Related Publications (6)

• 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.

  PMID: 33397713 BACKGROUND

• 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.

  PMID: 32749941 BACKGROUND

• 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.

  PMID: 30078506 BACKGROUND

• 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.

  PMID: 29449189 BACKGROUND

• 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.

  PMID: 31829442 BACKGROUND

• Li Y, Zhu C, Xie H, Chen Y, Lv W, Xie X, Wang X. Molecular profile-based recommendations for postoperative adjuvant therapy in early endometrial cancer with high-intermediate or intermediate risk: a Chinese randomized phase III trial (PROBEAT). J Gynecol Oncol. 2023 Mar;34(2):e37. doi: 10.3802/jgo.2023.34.e37. Epub 2023 Jan 10.

  PMID: 36659832 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Observation; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques; Combined Modality Therapy; Therapeutics

Study Officials

• Xinyu Wang, MD

  Women's Hospital School Of Medicine Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xinyu Wang, MD

CONTACT

+86-571-87061501; wangxinyu@zju.edu.cn

Yang Li, PhD

CONTACT

+86-571-87061501; li_yang@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: December 16, 2021
• First Posted: January 5, 2022
• Study Start: January 24, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (10)