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Endometrial Cancer Stage IPhase 3PORTEC-4aNCT03469674

PORTEC-4a: Molecular Profile-based Versus Standard Adjuvant Radiotherapy in Endometrial Cancer

A Phase 3 study testing Vaginal brachytherapy, External beam radiotherapy and Observation in people with Endometrial Cancer Stage I and Endometrial Cancer Stage II, run by Leiden University Medical Center at 31 sites in 8 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Vaginal brachytherapy, External beam radiotherapy and Observation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
550 participants
Where
31 sitesin 8 countries
Study dates
10 Jun 2016to 31 Dec 2028
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

31 sites in 8 countries.

31 sites in 8 countries

Netherlands15 sites

  • Academic Medical Center

    Amsterdam

  • NKI / Antoni van Leeuwenhoekhuis

    Amsterdam

  • Radiation Therapy Group

    Arnhem

  • Catharina Hospital

    Eindhoven

  • Zuidwest Radiotherapy Institute

    Flushing

  • University Medical Center Groningen

    Groningen

  • Radiotherapy Institute Friesland

    Leeuwarden

  • Leiden University Medical Center

    Leiden

  • MAASTRO radiation oncology clinic

    Maastricht

  • Radboud University Medical Center

    Nijmegen

  • ErasmusMC Cancer Center

    Rotterdam

  • Haaglanden Medical Center

    The Hague

  • Verbeeten institute

    Tilburg

  • University Medical Center Utrecht

    Utrecht

  • Isala Clinics

    Zwolle

Other trials in Netherlands

Germany7 sites

  • Sankt Gertrauden Krankenhaus

    Berlin

  • Kaiserswerther Diakonie

    Düsseldorf

  • Evang. Kliniken Essen-Mitte

    Essen

  • Universitatsklinikum Heidelberg

    Heidelberg

  • Universitätsklinikum Schleswig-Holstein, Campus Lübeck

    Lübeck

  • Rotkreuzklinikum München

    Münich

  • University Hospital

    Tübingen

Other trials in Germany

France3 sites

  • GINECO group - Institut Goustave Roussy

    Paris

  • Hôpital Européen Georges-Pompidou

    Paris

  • Hôpital Tenon

    Paris

Other trials in France

Ireland2 sites

  • CancerTrials Ireland - St James Hospital (SLRON SJH)

    Dublin

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

    Dublin

Other trials in Ireland

Austria1 site

  • Medical University, Vienna

    Vienna

Other trials in Austria

Belgium1 site

  • University Hospital Gent

    Ghent

Other trials in Belgium

Czechia1 site

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

    Prague

Other trials in Czechia

Switzerland1 site

  • Kantonsspital Frauenklinik Lucerne

    Lucerne

Other trials in Switzerland

About this study

Official title: Randomised Phase III Trial of Molecular Profile-based Versus Standard Recommendations for Adjuvant Radiotherapy for Women With Early Stage Endometrial Cancer: PORTEC-4a Trial

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.

Read the 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, LVSI and depth of invasion. Newer, both molecular-genetic (the cancer genome atlas subgroups) or immunohistochemistry-based (L1-CAM) risk factors have become available which are strongly related to outcomes and risk of cancer spread. In a comprehensive analysis of the PORTEC-1 and-2 biobank an integrated clinicopathological and molecular risk profile was determined which separated the current high-intermediate risk group of endometrial cancer in 3 separate groups (favourable, intermediate or unfavourable) with clearly separated outcomes, which is now prospectively tested in the clinic to determine adjuvant treatment. This is the first randomised trial using the molecular risk factors to assign adjuvant treatment for women with stage I-II high-intermediate risk endometrial cancer.

Being tested
Vaginal brachytherapy, External beam radiotherapy, Observation
Keywords
Radiotherapy, Vaginal brachytherapy, Molecular risk factors
Medical subject headings
Endometrial Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vaginal brachytherapyRadiation

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

  • External beam radiotherapyRadiation

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

  • ObservationOther

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

Study groups in NCT03469674
Study groupRoleWhat they receive
Molecular profile based treatmentExperimentalDetermination 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
Receives: Radiation: Vaginal brachytherapy; Radiation: External beam radiotherapy; Other: Observation
Vaginal brachytherapyActive comparatorAdjuvant vaginal brachytherapy (standard treatment)
Receives: Radiation: Vaginal brachytherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Vaginal recurrence

    Total vaginal recurrence and vaginal recurrence as first failure

    Measured: 5 years

Secondary outcomes (11)

  1. Adverse events

    Treatment-related symptoms according to CTCAE v 4.0

    Measured: 5 years

  2. Health-related cancer-specific quality of life

    Cancer-specific quality of life (European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQC-30) - clinically relevant changes on QLQC30 functioning scales, general quality of life and general cancer symptoms

    Measured: 5 years

  3. Endometrial cancer-related symptoms and quality of life

    Endometrial cancer-related specific symptoms (EORTC EN24 module)- clinically relevant changes on these scales (quite a bit/very much vs no or mild symptoms)

    Measured: 5 years

  4. Relapse-free survival

    Relapse-free survival (survival without relapse)

    Measured: 5 years

  5. Survival

    Overall survival (all-cause death)

    Measured: 5 years

  6. 5-year vaginal control including treatment for relapse

    Long-term local control including salvage treatment for local relapse

    Measured: 5 years

  7. Pelvic recurrence (total)

    Total pelvic recurrences

    Measured: 5 years

  8. Pelvic recurrence as first failure

    Pelvic recurrence as first failure

    Measured: 5 years

  9. Distant recurrence (total)

    Total distant recurrences

    Measured: 5 years

  10. Distant recurrence as first failure

    Distant recurrence as first failure

    Measured: 5 years

  11. 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

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Mar 2018
  2. Study start10 Jun 2016
  3. Primary completion31 Dec 2024 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
2:1 randomisation to adjuvant treatment assignment based on the integrated molecular risk profile or standard adjuvant vaginal brachytherapy
Masking
None (open label)
Enrolment
550 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03469674
Sponsor's protocol ID
P16.054
Other IDs
UL2011-5336, ISRCTN11659025, NTR5841
Acronym
PORTEC-4a
Status last verified
Oct 2023
First submitted
8 Mar 2018
Last updated
11 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Specifics will be decided and made public on website at a later stage, most probably from 5 years after final publication onwards

Publications

  • 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.

    PubMed 41449145

  • 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.

    PubMed 34540651

  • 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.

    PubMed 33046573

  • 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.

    PubMed 30078506

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Vaginal brachytherapy, External beam radiotherapy and Observation in people with Endometrial Cancer Stage I and Endometrial Cancer Stage II, run by Leiden University Medical Center at 31 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 11 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in Netherlands, Germany, France, Ireland, Austria and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Vaginal recurrence (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03469674, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2023.

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