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

NCT ID: NCT03469674

Last Updated: 2023-10-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

550 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-06-10

Study Completion Date

2028-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Endometrial Cancer Stage I Endometrial Cancer Stage II

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

2:1 randomisation to adjuvant treatment assignment based on the integrated molecular risk profile or standard adjuvant vaginal brachytherapy
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Evaluation of outcomes is done without information on randomised arm

Study Groups

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Molecular profile based treatment

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

Group Type EXPERIMENTAL

Vaginal brachytherapy

Intervention Type RADIATION

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

External beam radiotherapy

Intervention Type RADIATION

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

Observation

Intervention Type OTHER

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

Vaginal brachytherapy

Adjuvant vaginal brachytherapy (standard treatment)

Group Type ACTIVE_COMPARATOR

Vaginal brachytherapy

Intervention Type RADIATION

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

Interventions

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Vaginal brachytherapy

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

Intervention Type RADIATION

External beam radiotherapy

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

Intervention Type RADIATION

Observation

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

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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):

1. Stage IA, grade 3 (any age, with or without LVSI)
2. Stage IB, grade 1 or 2 and age \>60 years
3. Stage IB, grade 1-2 with documented LVSI
4. Stage IB, grade 3 without LVSI
5. Stage II (microscopic), grade 1
* World Health Organization (WHO)-performance status 0-2
* Written informed consent

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Dutch Cancer Society

OTHER

Sponsor Role collaborator

Comprehensive Cancer Centre The Netherlands

OTHER

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Carien Creutzberg

Chief Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Carien L. Creutzberg, MD, PhD

Role: STUDY_CHAIR

Leiden University Medical Center, Dept of Radiation Oncology

Remi A. Nout, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

ErasmusMC Dept of Radiation Oncology

Anne-Sophie van den Heerik, MD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center, Dept of Radiation Oncology

Locations

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Medical University, Vienna

Vienna, , Austria

Site Status

University Hospital Gent

Ghent, , Belgium

Site Status

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

Prague, , Czechia

Site Status

GINECO group - Institut Goustave Roussy

Paris, , France

Site Status

Hôpital Européen Georges-Pompidou

Paris, , France

Site Status

Hôpital Tenon

Paris, , France

Site Status

Sankt Gertrauden Krankenhaus

Berlin, , Germany

Site Status

Kaiserswerther Diakonie

Düsseldorf, , Germany

Site Status

Evang. Kliniken Essen-Mitte

Essen, , Germany

Site Status

Universitatsklinikum Heidelberg

Heidelberg, , Germany

Site Status

Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Lübeck, , Germany

Site Status

Rotkreuzklinikum München

Münich, , Germany

Site Status

University Hospital

Tübingen, , Germany

Site Status

CancerTrials Ireland - St James Hospital (SLRON SJH)

Dublin, , Ireland

Site Status

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

Dublin, , Ireland

Site Status

Academic Medical Center

Amsterdam, , Netherlands

Site Status

NKI / Antoni van Leeuwenhoekhuis

Amsterdam, , Netherlands

Site Status

Radiation Therapy Group

Arnhem, , Netherlands

Site Status

Catharina Hospital

Eindhoven, , Netherlands

Site Status

Zuidwest Radiotherapy Institute

Flushing, , Netherlands

Site Status

University Medical Center Groningen

Groningen, , Netherlands

Site Status

Radiotherapy Institute Friesland

Leeuwarden, , Netherlands

Site Status

Leiden University Medical Center

Leiden, , Netherlands

Site Status

MAASTRO radiation oncology clinic

Maastricht, , Netherlands

Site Status

Radboud University Medical Center

Nijmegen, , Netherlands

Site Status

ErasmusMC Cancer Center

Rotterdam, , Netherlands

Site Status

Haaglanden Medical Center

The Hague, , Netherlands

Site Status

Verbeeten institute

Tilburg, , Netherlands

Site Status

University Medical Center Utrecht

Utrecht, , Netherlands

Site Status

Isala Clinics

Zwolle, , Netherlands

Site Status

Kantonsspital Frauenklinik Lucerne

Lucerne, , Switzerland

Site Status

Countries

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Austria Belgium Czechia France Germany Ireland Netherlands Switzerland

References

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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.

Reference Type DERIVED
PMID: 34540651 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33046573 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30078506 (View on PubMed)

Related Links

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Other Identifiers

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UL2011-5336

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ISRCTN11659025

Identifier Type: REGISTRY

Identifier Source: secondary_id

NTR5841

Identifier Type: REGISTRY

Identifier Source: secondary_id

P16.054

Identifier Type: -

Identifier Source: org_study_id

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