PROfiling Based Endometrial Cancer Adjuvant Therapy

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Лучевая терапия 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
• Лучевая терапия External beam radiotherapy
  External beam pelvic radiotherapy on a linear accelerator, 45-50 Gy in 25-28 out-patients sessions
• Другое Observation
  No adjuvant therapy, but active follow-up and quality of life questionnaires as in the groups who have adjuvant treatment
• Комбинированный продукт Chemoradiation therapy
  4 adjuvant cycles carboplatin and paclitaxel followed by External beam pelvic radiotherapy (45-50 Gy )

Первичные конечные точки

• Total recurrence [Срок оценки: 3 years]

Вторичные конечные точки (5)

• Relapse-free survival [Срок оценки: 3 years, 5 years]
• Survival [Срок оценки: 3 years, 5 years]
• Adverse events [Срок оценки: 3 years, 5 years]
• Health-related cancer-specific quality of life [Срок оценки: 3 years, 5 years]
• Endometrial cancer related health care costs [Срок оценки: 3 years, 5 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 10 центров

• Tongji Hospital, Huazhong University of Science and Technology — Ухань
• Qilu Hospital of Shandong University — Цзинань
• Women's Hospital School of Medicine Zhejiang University — Ханчжоу
• Peking University Peoples Hospital — Пекин
• Xiangya Hospital of Central South University — Чанша
• Sun Yat-Sen University Cancer Hospital — Гуанчжоу
• Ningbo First Hospital — Ningbo
• Ningbo Women and Children's Hospital — Ningbo
• … и ещё 2 центра

Публикации

• 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 endometria PMID 33397713
• 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 PMID 32749941
• 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. PMID 30078506
• 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 chemoradi PMID 29449189
• 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
• 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

Идентификаторы

NCT: NCT05179447 · IRB-20210340-R

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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