Clinical trial NCT03469674: PORTEC-4a: Molecular Profile-based Versus Standard Adjuvant Radiotherapy in Endometrial Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Endometrial Cancer Stage I
Endometrial Cancer Stage II
Keywords: Radiotherapy
Vaginal brachytherapy
Molecular risk factors
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Dutch Cancer Society
name: Comprehensive Cancer Centre The Netherlands
First posted: 2018-03-19
Enrollment: 550
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2:1 randomisation to adjuvant treatment assignment based on the integrated molecular risk profile or standard adjuvant vaginal brachytherapy
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Vaginal recurrence
timeFrame: 5 years
Secondary outcomes:
measure: Adverse events
timeFrame: 5 years
measure: Health-related cancer-specific quality of life
timeFrame: 5 years
measure: Endometrial cancer-related symptoms and quality of life
timeFrame: 5 years
measure: Relapse-free survival
timeFrame: 5 years
measure: Survival
timeFrame: 5 years
measure: 5-year vaginal control including treatment for relapse
timeFrame: 5 years
measure: Pelvic recurrence (total)
timeFrame: 5 years
measure: Pelvic recurrence as first failure
timeFrame: 5 years
measure: Distant recurrence (total)
timeFrame: 5 years
measure: Distant recurrence as first failure
timeFrame: 5 years
measure: Endometrial cancer related health care costs
timeFrame: 5 years
Other outcomes:
measure: Recurrence (vaginal and total) per risk profile
timeFrame: 5 years
Locations:
city: Vienna
country: Austria
facility: Medical University, Vienna
city: Gent
country: Belgium
facility: University Hospital Gent
city: Praha
country: Czechia
facility: CEEGOG, General Faculty Hospital and First Faculty of Medicine, Charles University, Prague
city: Paris
country: France
facility: GINECO group - Institut Goustave Roussy
city: Paris
country: France
facility: Hôpital Européen Georges-Pompidou
city: Paris
country: France
facility: Hôpital Tenon
city: Berlin
country: Germany
facility: Sankt Gertrauden Krankenhaus
city: Düsseldorf
country: Germany
facility: Kaiserswerther Diakonie
city: Essen
country: Germany
facility: Evang. Kliniken Essen-Mitte
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Lübeck
city: Münich
country: Germany
facility: Rotkreuzklinikum München
city: Tübingen
country: Germany
facility: University Hospital
city: Dublin
country: Ireland
facility: CancerTrials Ireland - St James Hospital (SLRON SJH)
city: Dublin
country: Ireland
facility: CancerTrials Ireland - St Luke's Hospital (SLRON SLH)
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Amsterdam
country: Netherlands
facility: NKI / Antoni van Leeuwenhoekhuis
city: Arnhem
country: Netherlands
facility: Radiation Therapy Group
city: Den Haag
country: Netherlands
facility: Haaglanden Medical Center
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leeuwarden
country: Netherlands
facility: Radiotherapy Institute Friesland
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: MAASTRO radiation oncology clinic
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Rotterdam
country: Netherlands
facility: ErasmusMC Cancer Center
city: Tilburg
country: Netherlands
facility: Verbeeten institute
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Vlissingen
country: Netherlands
facility: Zuidwest Radiotherapy Institute
city: Zwolle
country: Netherlands
facility: Isala Clinics
city: Lucerne
country: Switzerland
facility: Kantonsspital Frauenklinik Lucerne
Study officials:
affiliation: Leiden University Medical Center, Dept of Radiation Oncology
name: Carien L. Creutzberg, MD, PhD
role: STUDY_CHAIR
affiliation: ErasmusMC Dept of Radiation Oncology
name: Remi A. Nout, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Leiden University Medical Center, Dept of Radiation Oncology
name: Anne-Sophie van den Heerik, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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.