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Study of Early Stage Endometrial Cancer Based on Molecular Classification and Traditional Risk Stratification to Guide Adjuvant Radiotherapy Decisions

Primary Purpose

Endometrial Cancer, Adjuvant Radiotherapy, Molecular Classification

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Vaginal brachytherapy
Pelvic external beam radiotherapy
Observation
Chemotherapy
Sponsored by
Peking Union Medical College Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Endometrial Cancer focused on measuring Endometrial Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Women aged 18-75.
  2. Patients with newly histologically confirmed Endometrioid adenocarcinoma.
  3. ECOG score 0-2
  4. Surgery consisting of a total hysterectomy and bilateral salpingo-oophorectomy, pelvic lymphadenectomy or sentinel lymph node biopsy, with or without para-aortic lymphadenectomy, oophorectomy

  5. Patients with FIGO staging(2009 edition) I or II and meet one of the following conditions:

    1. Stage IA G1-2 with massive LVSI+ or age ≥ 60 years
    2. Stage IA G3, regardless of LVSI status
    3. Stage IB G1-3, regardless of LVSI status
    4. Stage II, regardless of tumor grade and LVSI status
  6. Patients can understand the study protocol and voluntarily participate in the study, and give written informed consent before treatment.

Exclusion Criteria:

  1. Not FIGO stage I-II.
  2. Residual tumor or positive margin.
  3. Mixed carcinoma, sarcoma or carcinosarcoma
  4. Previous history of malignant tumor
  5. Previous history of pelvic radiotherapy
  6. The interval between surgery and radiotherapy is more than 12 weeks.
  7. With serious medical complications, such as heart disease, lung disease and other diseases that cannot tolerate the whole course of radiotherapy

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Molecular classification based treatment

    Conventional risk stratification based treatment

    Arm Description

    Establishment of molecular-clinicopathological classification to make adjuvant treatment decisions: observation for favourable group; vaginal brachytherapy(VBT) for intermediate group; external beam radiotherapy(EBRT) for unfavourable group. Molecular-clinicopathological classification strategy：Favourable group：POLE-mutated. CTNNB1(wide-type)with IA (G1-3) or IB(G1-2)and LVSI(lymph-vascular space invasion) focal/-. Intermediate group：MMRD and LVSI focal/-. CTNNB1(wide-type) and IB(G3) or II with LVSI focal/-. CTNNB1-mutated and IA(G1-3) or IB (G1-2) with LVSI focal/-. Unfavourable group: TP53 mutation. CTNNB1-mutated and IB (G3) or II. Substantial LVSI.

    Adjuvant vaginal brachytherapy alone for intermediate risk patients (IA G1-2 with LVSI present or age>60, IA G3 or IB G1-2 regardless of LVSI status). EBRT for high-intermediate risk (stage I B with G3, or stage II)

    Outcomes

    Primary Outcome Measures

    Loco-regional recurrence (LRR)
    Loco-regional recurrence (LRR) is defined as the first recurrence in the vagina or pelvic cavity during follow-up, which was confirmed by imaging examination or biopsy pathology.

    Secondary Outcome Measures

    Failure free survival(FFS)
    FFS is defined as the time from randomization to recurrence,distant metastasis or death from any cause,whichever is first.
    Overall survical(OS)
    Overall survival is calculated from randomization to death from any cause.
    Cumulative vaginal recurrence
    Recurrence in the vaginal area during follow-up
    Cumulative pelvic recurrence
    Recurrence in the pelvic area, including the vagina, during follow-up
    Distance metastasis(DM)
    Distant metastasis (such as bone, lung, liver, brain, non-pelvic regional lymph node metastasis).
    De-escalation rate of treatment
    Comparison of the proportion of patients in two groups with the same clinicopathologic factors (FIGO, G, LVSI, age) downgraded from EBRT to VBT or from adjuvant radiotherapy (EBRT or VBT) to observation.
    Health-related cancer-specific quality of life
    General quality of life and general cancer related symptoms is accessed by Quality of Life Core Questionnaire (QLQC-30), ,scored as quite a bit/very much vs no or mild symptoms
    Incidence of Acute and lateToxicities
    Acute radiation enteritis, radiation cystitis, radiation lymphopenia, late radiation enteritis, radiation cystitis, vaginal stenosis or shortening, lymphedema, bone marrow suppression according to CTCAE v 5.0.
    Endometrial cancer related health care costs
    All hospital based health care costs used with primary treatment or during follow-up for treatment of adverse events and/or treatment for relapse.

    Full Information

    First Posted
    August 30, 2022
    Last Updated
    November 20, 2022
    Sponsor
    Peking Union Medical College Hospital
    Collaborators
    Xijing Hospital, Air Force Medical University of PLA, The Second Affiliated Hospital of Dalian Medical University, The second hospital Affiliated by Jilin University, First Affiliated Hospital Xi'an Jiaotong University, The Affiliated Hospital of Inner Mongolia Medical University, Third Affiliated Hospital of Xinjiang Medical University, Peking University First Hospital, The 940th Hospital of Joint Logistics Support Force，PLA., Xiangya Hospital of Central South University, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05524389
    Brief Title
    Study of Early Stage Endometrial Cancer Based on Molecular Classification and Traditional Risk Stratification to Guide Adjuvant Radiotherapy Decisions
    Official Title
    A Prospective Multicentre Phase III Randomised Open Clinical Study of Early Stage Endometrial Cancer Based on Molecular Classification and Traditional Risk Stratification to Guide Adjuvant Radiotherapy Decisions
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 1, 2022 (Anticipated)
    Primary Completion Date
    December 1, 2026 (Anticipated)
    Study Completion Date
    June 30, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Peking Union Medical College Hospital
    Collaborators
    Xijing Hospital, Air Force Medical University of PLA, The Second Affiliated Hospital of Dalian Medical University, The second hospital Affiliated by Jilin University, First Affiliated Hospital Xi'an Jiaotong University, The Affiliated Hospital of Inner Mongolia Medical University, Third Affiliated Hospital of Xinjiang Medical University, Peking University First Hospital, The 940th Hospital of Joint Logistics Support Force，PLA., Xiangya Hospital of Central South University, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of this study is to compare the efficacy and toxicity of early stage endometrial cancer based on molecular classification and conventional risk stratification adjuvant therapy decision-making, and to provide high-quality evidence-based medical evidence for individualized adjuvant therapy selection under the guidance of fine stratification system of endometrial cancer.
    Detailed Description
    This is an investigator-initiated prospective, national multicentre, phase III, randomised, open, non-inferiority clinical study. The study hypothesis is that adjuvant radiotherapy decision for early-stage endometrial cancer which is based on molecular classification can achieve de-escalation of adjuvant treatment without reducing local tumour control and survival, thereby potentially further reducing radiotherapy-related toxicity and improving quality of life, compared to using conventional risk stratification. The primary endpoint of this study is the 3-year local recurrence rate.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Endometrial Cancer, Adjuvant Radiotherapy, Molecular Classification
    Keywords
    Endometrial Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    624 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Molecular classification based treatment
    Arm Type
    Experimental
    Arm Description
    Establishment of molecular-clinicopathological classification to make adjuvant treatment decisions: observation for favourable group; vaginal brachytherapy(VBT) for intermediate group; external beam radiotherapy(EBRT) for unfavourable group. Molecular-clinicopathological classification strategy：Favourable group：POLE-mutated. CTNNB1(wide-type)with IA (G1-3) or IB(G1-2)and LVSI(lymph-vascular space invasion) focal/-. Intermediate group：MMRD and LVSI focal/-. CTNNB1(wide-type) and IB(G3) or II with LVSI focal/-. CTNNB1-mutated and IA(G1-3) or IB (G1-2) with LVSI focal/-. Unfavourable group: TP53 mutation. CTNNB1-mutated and IB (G3) or II. Substantial LVSI.
    Arm Title
    Conventional risk stratification based treatment
    Arm Type
    Active Comparator
    Arm Description
    Adjuvant vaginal brachytherapy alone for intermediate risk patients (IA G1-2 with LVSI present or age>60, IA G3 or IB G1-2 regardless of LVSI status). EBRT for high-intermediate risk (stage I B with G3, or stage II)
    Intervention Type
    Radiation
    Intervention Name(s)
    Vaginal brachytherapy
    Other Intervention Name(s)
    VBT
    Intervention Description
    High-dose rate vaginal brachytherapy (VBT) was delivered with a vaginal cylinder.For VBT administered alone, the dose is recommended: 3 fractions of 7 Gy or 5 fractions of 6 Gy or 6 fractions of 5 Gy. For VBT administered after completion of EBRT: 2-3 fractions of 4-6 Gy.
    Intervention Type
    Radiation
    Intervention Name(s)
    Pelvic external beam radiotherapy
    Other Intervention Name(s)
    Pelvic EBRT
    Intervention Description
    EBRT was delivered to the pelvic area using a total dose of 45-50.4Gy in 25-28 fractions over 5-6 weeks with the intensity-modulated radiotherapy (IMRT) technique, three-dimensional conformal radiotherapy (3D-CRT) modality
    Intervention Type
    Other
    Intervention Name(s)
    Observation
    Intervention Description
    No radiotherapy is administrated, but active follow-up and quality of life questionnaires is needed after surgery.
    Intervention Type
    Drug
    Intervention Name(s)
    Chemotherapy
    Intervention Description
    Intravenous concurrent or sequential adjuvant chemotherapy consists of carboplatin/paclitaxel, cisplatin/doxorubicin or cisplatin/doxorubicin/paclitaxel, etc.
    Primary Outcome Measure Information:
    Title
    Loco-regional recurrence (LRR)
    Description
    Loco-regional recurrence (LRR) is defined as the first recurrence in the vagina or pelvic cavity during follow-up, which was confirmed by imaging examination or biopsy pathology.
    Time Frame
    3-year
    Secondary Outcome Measure Information:
    Title
    Failure free survival(FFS)
    Description
    FFS is defined as the time from randomization to recurrence,distant metastasis or death from any cause,whichever is first.
    Time Frame
    3-year,5-year
    Title
    Overall survical(OS)
    Description
    Overall survival is calculated from randomization to death from any cause.
    Time Frame
    3-year,5-year
    Title
    Cumulative vaginal recurrence
    Description
    Recurrence in the vaginal area during follow-up
    Time Frame
    3-year,5-year
    Title
    Cumulative pelvic recurrence
    Description
    Recurrence in the pelvic area, including the vagina, during follow-up
    Time Frame
    3-year,5-year
    Title
    Distance metastasis(DM)
    Description
    Distant metastasis (such as bone, lung, liver, brain, non-pelvic regional lymph node metastasis).
    Time Frame
    3-year,5-year
    Title
    De-escalation rate of treatment
    Description
    Comparison of the proportion of patients in two groups with the same clinicopathologic factors (FIGO, G, LVSI, age) downgraded from EBRT to VBT or from adjuvant radiotherapy (EBRT or VBT) to observation.
    Time Frame
    3-year
    Title
    Health-related cancer-specific quality of life
    Description
    General quality of life and general cancer related symptoms is accessed by Quality of Life Core Questionnaire (QLQC-30), ,scored as quite a bit/very much vs no or mild symptoms
    Time Frame
    3-year,5-year
    Title
    Incidence of Acute and lateToxicities
    Description
    Acute radiation enteritis, radiation cystitis, radiation lymphopenia, late radiation enteritis, radiation cystitis, vaginal stenosis or shortening, lymphedema, bone marrow suppression according to CTCAE v 5.0.
    Time Frame
    3-year,5-year
    Title
    Endometrial cancer related health care costs
    Description
    All hospital based health care costs used with primary treatment or during follow-up for treatment of adverse events and/or treatment for relapse.
    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: Women aged 18-75. Patients with newly histologically confirmed Endometrioid adenocarcinoma. ECOG score 0-2 Surgery consisting of a total hysterectomy and bilateral salpingo-oophorectomy, pelvic lymphadenectomy or sentinel lymph node biopsy, with or without para-aortic lymphadenectomy, oophorectomy Patients with FIGO staging(2009 edition) I or II and meet one of the following conditions: Stage IA G1-2 with massive LVSI+ or age ≥ 60 years Stage IA G3, regardless of LVSI status Stage IB G1-3, regardless of LVSI status Stage II, regardless of tumor grade and LVSI status Patients can understand the study protocol and voluntarily participate in the study, and give written informed consent before treatment. Exclusion Criteria: Not FIGO stage I-II. Residual tumor or positive margin. Mixed carcinoma, sarcoma or carcinosarcoma Previous history of malignant tumor Previous history of pelvic radiotherapy The interval between surgery and radiotherapy is more than 12 weeks. With serious medical complications, such as heart disease, lung disease and other diseases that cannot tolerate the whole course of radiotherapy
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Xiaorong Hou, PhD
    Phone
    +86-13811963013
    Email
    hxr_pumch@163.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Xiaorong Hou, PhD
    Phone
    +86-01069155487
    Email
    hxr_pumch@163.com

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    34779587
    Citation
    Ren K, Wang W, Sun S, Hou X, Hu K, Zhang F. Recurrent patterns after postoperative radiotherapy for early stage endometrial cancer: A competing risk analysis model. Cancer Med. 2022 Jan;11(1):257-267. doi: 10.1002/cam4.4423. Epub 2021 Nov 15.
    Results Reference
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