NCT03469674

Brief Summary

This is prospective, multicenter, randomised phase III trial among women with endometrial cancer with high-intermediate risk features to investigate the role of an integrated clinicopathological and molecular risk profile to determine if participants should receive no adjuvant therapy, vaginal brachytherapy or external beam radiotherapy based on a favourable, intermediate or unfavourable profile as compared to standard adjuvant vaginal brachytherapy.

Trial Health

82
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
550

participants targeted

Target at P75+ for phase_3

Timeline
32mo left

Started Jun 2016

Longer than P75 for phase_3

Geographic Reach
8 countries

31 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress79%
Jun 2016Dec 2028

Study Start

First participant enrolled

June 10, 2016

Completed
1.7 years until next milestone

First Submitted

Initial submission to the registry

March 8, 2018

Completed
11 days until next milestone

First Posted

Study publicly available on registry

March 19, 2018

Completed
6.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2024

Completed
4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2028

Expected
Last Updated

October 11, 2023

Status Verified

October 1, 2023

Enrollment Period

8.6 years

First QC Date

March 8, 2018

Last Update Submit

October 10, 2023

Conditions

Endometrial Cancer Stage IEndometrial Cancer Stage II

Keywords

RadiotherapyVaginal brachytherapyMolecular risk factors

Outcome Measures

Primary Outcomes (1)

  • Vaginal recurrence

    Total vaginal recurrence and vaginal recurrence as first failure

    5 years

Secondary Outcomes (11)

  • Adverse events

    5 years

  • Health-related cancer-specific quality of life

    5 years

  • Endometrial cancer-related symptoms and quality of life

    5 years

  • Relapse-free survival

    5 years

  • Survival

    5 years

  • +6 more secondary outcomes

Other Outcomes (1)

  • Recurrence (vaginal and total) per risk profile

    5 years

Study Arms (2)

Molecular profile based treatment

EXPERIMENTAL

Determination of the integrated clinicopathological and molecular profile to determine adjuvant treatment: observation for favourable profile; vaginal brachytherapy for intermediate profile; external beam radiotherapy for unfavourable profile

Radiation: Vaginal brachytherapyRadiation: External beam radiotherapyOther: Observation

Vaginal brachytherapy

ACTIVE COMPARATOR

Adjuvant vaginal brachytherapy (standard treatment)

Radiation: Vaginal brachytherapy

Interventions

Vaginal brachytherapyRADIATION

Internal radiation of the vaginal vault using a vaginal cylinder, 21 Gy in 3 out-patient sessions over 2 weeks

Molecular profile based treatmentVaginal brachytherapy
External beam radiotherapyRADIATION

External beam pelvic radiotherapy on a linear accelerator, 48.6 Gy in 27 out-patients sessions over 5.5 weeks

Molecular profile based treatment
ObservationOTHER

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

Molecular profile based treatment

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed endometrioid type endometrial carcinoma, International Federation of Gynecology and Obstetrics (FIGO) 2009 stage I, with one of the following combinations of stage, grade, age, and lymph-vascular space invasion (LVSI):
  • Stage IA, grade 3 (any age, with or without LVSI)
  • Stage IB, grade 1 or 2 and age \>60 years
  • Stage IB, grade 1-2 with documented LVSI
  • Stage IB, grade 3 without LVSI
  • Stage II (microscopic), grade 1
  • World Health Organization (WHO)-performance status 0-2
  • Written informed consent

You may not qualify if:

  • 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) \< 5 yrs
  • Previous pelvic radiotherapy
  • Expected interval between the operation and start of radiotherapy exceeding 8 weeks

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (31)

Medical University, Vienna

Vienna, Austria

Location

University Hospital Gent

Ghent, Belgium

Location

CEEGOG, General Faculty Hospital and First Faculty of Medicine, Charles University, Prague

Prague, Czechia

Location

GINECO group - Institut Goustave Roussy

Paris, France

Location

Hôpital Européen Georges-Pompidou

Paris, France

Location

Hôpital Tenon

Paris, France

Location

Sankt Gertrauden Krankenhaus

Berlin, Germany

Location

Kaiserswerther Diakonie

Düsseldorf, Germany

Location

Evang. Kliniken Essen-Mitte

Essen, Germany

Location

Universitatsklinikum Heidelberg

Heidelberg, Germany

Location

Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Lübeck, Germany

Location

Rotkreuzklinikum München

Münich, Germany

Location

University Hospital

Tübingen, Germany

Location

CancerTrials Ireland - St James Hospital (SLRON SJH)

Dublin, Ireland

Location

CancerTrials Ireland - St Luke's Hospital (SLRON SLH)

Dublin, Ireland

Location

Academic Medical Center

Amsterdam, Netherlands

Location

NKI / Antoni van Leeuwenhoekhuis

Amsterdam, Netherlands

Location

Radiation Therapy Group

Arnhem, Netherlands

Location

Catharina Hospital

Eindhoven, Netherlands

Location

Zuidwest Radiotherapy Institute

Flushing, Netherlands

Location

University Medical Center Groningen

Groningen, Netherlands

Location

Radiotherapy Institute Friesland

Leeuwarden, Netherlands

Location

Leiden University Medical Center

Leiden, Netherlands

Location

MAASTRO radiation oncology clinic

Maastricht, Netherlands

Location

Radboud University Medical Center

Nijmegen, Netherlands

Location

ErasmusMC Cancer Center

Rotterdam, Netherlands

Location

Haaglanden Medical Center

The Hague, Netherlands

Location

Verbeeten institute

Tilburg, Netherlands

Location

University Medical Center Utrecht

Utrecht, Netherlands

Location

Isala Clinics

Zwolle, Netherlands

Location

Kantonsspital Frauenklinik Lucerne

Lucerne, Switzerland

Location

Related Publications (4)

  • van den Heerik ASVM, Horeweg N, Haverkort MAD, Kuijsters N, Kommoss S, Koppe FLA, Nowee ME, Westerveld H, De Jong MAA, Fruhauf F, Cnossen JS, Mens JWM, Beukema JC, Chargari C, Gillham C, Jurgenliemk-Schulz IM, Vandecasteele K, Hamann M, Kiderlen M, Staebler A, Nijman HW, Wortman BG, Asteinidou E, de Boer SM, van den Hout WB, Verhoeven-Adema KW, Nout RA, Putter H, Bosse T, Creutzberg CL. Molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer (PORTEC-4a): results of a randomised, open-label, phase 3, multicentre, non-inferiority trial. Lancet Oncol. 2026 Jan;27(1):23-35. doi: 10.1016/S1470-2045(25)00612-6.

    PMID: 41449145DERIVED

  • Nero C, Ciccarone F, Pietragalla A, Duranti S, Daniele G, Scambia G, Lorusso D. Adjuvant Treatment Recommendations in Early-Stage Endometrial Cancer: What Changes With the Introduction of The Integrated Molecular-Based Risk Assessment. Front Oncol. 2021 Sep 1;11:612450. doi: 10.3389/fonc.2021.612450. eCollection 2021.

    PMID: 34540651DERIVED

  • van den Heerik ASVM, Horeweg N, Nout RA, Lutgens LCHW, van der Steen-Banasik EM, Westerveld GH, van den Berg HA, Slot A, Koppe FLA, Kommoss S, Mens JWM, Nowee ME, Bijmolt S, Cibula D, Stam TC, Jurgenliemk-Schulz IM, Snyers A, Hamann M, Zwanenburg AG, Coen VLMA, Vandecasteele K, Gillham C, Chargari C, Verhoeven-Adema KW, Putter H, van den Hout WB, Wortman BG, Nijman HW, Bosse T, Creutzberg CL. PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer. Int J Gynecol Cancer. 2020 Dec;30(12):2002-2007. doi: 10.1136/ijgc-2020-001929. Epub 2020 Oct 12.

    PMID: 33046573DERIVED

  • 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: 30078506DERIVED

Related Links

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Observation

Condition Hierarchy (Ancestors)

Uterine NeoplasmsGenital Neoplasms, FemaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsUterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Diseases

Intervention Hierarchy (Ancestors)

MethodsInvestigative Techniques

Study Officials

  • Carien L. Creutzberg, MD, PhD

    Leiden University Medical Center, Dept of Radiation Oncology

    STUDY CHAIR

  • Remi A. Nout, MD, PhD

    ErasmusMC Dept of Radiation Oncology

    PRINCIPAL INVESTIGATOR

  • Anne-Sophie van den Heerik, MD

    Leiden University Medical Center, Dept of Radiation Oncology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Masking Details
Evaluation of outcomes is done without information on randomised arm
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 2:1 randomisation to adjuvant treatment assignment based on the integrated molecular risk profile or standard adjuvant vaginal brachytherapy
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Chief Investigator

Study Record Dates

First Submitted

March 8, 2018

First Posted

March 19, 2018

Study Start

June 10, 2016

Primary Completion

December 31, 2024

Study Completion (Estimated)

December 31, 2028

Last Updated

October 11, 2023

Record last verified: 2023-10

Data Sharing

IPD Sharing
Will share

Specifics will be decided and made public on website at a later stage, most probably from 5 years after final publication onwards

Shared Documents
STUDY PROTOCOL, SAP, CSR
Time Frame
From 5 years after final publication onwards
Access Criteria
Upon written application with a clear decription of aim, methods and analysis plan, publication plan, after approval from the study team

Locations

IE(2)FR(3)BE(1)DE(7)CZ(1)CH(1)NL(15)AU(1)