Back to resultsPROfiling Based Endometrial Cancer Adjuvant Therapy (PROBEAT)
Primary Purpose
Endometrial Cancer Stage I, Endometrial Cancer Stage II
Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Vaginal brachytherapy
External beam radiotherapy
Observation
Chemoradiation therapy
Sponsored by
About this trial
This is an interventional treatment trial for Endometrial Cancer Stage I
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- Tongji Hospital, Huazhong University of Science and Technology
- Qilu Hospital of Shandong University
- Women's Hospital School of Medicine Zhejiang UniversityRecruiting
- Peking University Peoples Hospital
- Sun Yat-Sen University Cancer Hospital
- Obstetrics & Gynecology Hospital of Fudan University
- Shanghai First Maternity and Infant Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Molecular profile based treatment
Radiotherapy
Arm Description
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.
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)
Outcomes
Primary Outcome Measures
Total recurrence
Vaginal, pelvic or distant recurrence as first failure
Secondary Outcome Measures
Relapse-free survival
Relapse-free survival (survival without relapse)
Survival
Overall survival (all-cause death)
Adverse events
Treatment-related symptoms according to CTCAE v 5.0
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
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
Full Information
NCT ID
NCT05179447
First Posted
December 16, 2021
Last Updated
April 19, 2022
Sponsor
Women's Hospital School Of Medicine Zhejiang University
Collaborators
Tongji Hospital, Qilu Hospital of Shandong University, Obstetrics & Gynecology Hospital of Fudan University, Sun Yat-sen University, Peking University People's Hospital, Shanghai First Maternity and Infant Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05179447
Brief Title
PROfiling Based Endometrial Cancer Adjuvant Therapy
Acronym
PROBEAT
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
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 24, 2022 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
January 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Women's Hospital School Of Medicine Zhejiang University
Collaborators
Tongji Hospital, Qilu Hospital of Shandong University, Obstetrics & Gynecology Hospital of Fudan University, Sun Yat-sen University, Peking University People's Hospital, Shanghai First Maternity and Infant Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endometrial Cancer Stage I, Endometrial Cancer Stage II
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
590 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Molecular profile based treatment
Arm Type
Experimental
Arm Description
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.
Arm Title
Radiotherapy
Arm Type
Active Comparator
Arm Description
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)
Intervention Type
Radiation
Intervention Name(s)
Vaginal brachytherapy
Intervention Description
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
Intervention Type
Radiation
Intervention Name(s)
External beam radiotherapy
Intervention Description
External beam pelvic radiotherapy on a linear accelerator, 45-50 Gy in 25-28 out-patients sessions
Intervention Type
Other
Intervention Name(s)
Observation
Intervention Description
No adjuvant therapy, but active follow-up and quality of life questionnaires as in the groups who have adjuvant treatment
Intervention Type
Combination Product
Intervention Name(s)
Chemoradiation therapy
Intervention Description
4 adjuvant cycles carboplatin and paclitaxel followed by External beam pelvic radiotherapy (45-50 Gy )
Primary Outcome Measure Information:
Title
Total recurrence
Description
Vaginal, pelvic or distant recurrence as first failure
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Relapse-free survival
Description
Relapse-free survival (survival without relapse)
Time Frame
3 years, 5 years
Title
Survival
Description
Overall survival (all-cause death)
Time Frame
3 years, 5 years
Title
Adverse events
Description
Treatment-related symptoms according to CTCAE v 5.0
Time Frame
3 years, 5 years
Title
Health-related cancer-specific quality of life
Description
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
Time Frame
3 years, 5 years
Title
Endometrial cancer related health care costs
Description
All hospital based health care costs used with primary treatment or during followup for treatment of adverse events and/or treatment for relapse
Time Frame
3 years, 5 years
Other Pre-specified Outcome Measures:
Title
Recurrence (vaginal and total) per risk profile
Description
Vaginal, pelvic and distant relapse split by risk profile and compared between the 2 arms
Time Frame
3 years, 5 years
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xinyu Wang, MD
Phone
+86-571-87061501
Email
wangxinyu@zju.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Yang Li, PhD
Phone
+86-571-87061501
Email
li_yang@zju.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xinyu Wang, MD
Organizational Affiliation
Women's Hospital School Of Medicine Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tongji Hospital, Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gang Chen
Email
gumpc@126.com
First Name & Middle Initial & Last Name & Degree
Ding Ma
Facility Name
Qilu Hospital of Shandong University
City
Jinan
State/Province
Shandong
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jie Jiang
Email
qljiangjie@aliyun.com
First Name & Middle Initial & Last Name & Degree
Beihua Kong
Facility Name
Women's Hospital School of Medicine Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xinyu Wang, MD
Phone
+86-571-87061501
Email
wangxinyu@zju.edu.cn
First Name & Middle Initial & Last Name & Degree
Yang Li
Phone
+86-571-87061501
Email
li_yang@zju.edu.cn
Facility Name
Peking University Peoples Hospital
City
Beijing
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhiqi Wang
First Name & Middle Initial & Last Name & Degree
Zhiqi Wang
Facility Name
Sun Yat-Sen University Cancer Hospital
City
Guangzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yanling Feng
First Name & Middle Initial & Last Name & Degree
Jihong Liu
Facility Name
Obstetrics & Gynecology Hospital of Fudan University
City
Shanghai
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaojun Chen
Email
cxjlhjj@163.com
First Name & Middle Initial & Last Name & Degree
Xiaojun Chen
Facility Name
Shanghai First Maternity and Infant Hospital
City
Shanghai
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaoping Wan
First Name & Middle Initial & Last Name & Degree
Xiaoping Wan
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33397713
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.
Results Reference
background
PubMed Identifier
32749941
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.
Results Reference
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PubMed Identifier
30078506
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.
Results Reference
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PubMed Identifier
29449189
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.
Results Reference
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PubMed Identifier
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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.
Results Reference
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PROfiling Based Endometrial Cancer Adjuvant Therapy
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