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

Phase 3

Active, not recruiting

• Conditions: Endometrial Cancer Stage I; Endometrial Cancer Stage II
• Interventions: Radiation: Vaginal brachytherapy; Radiation: External beam radiotherapy; Other: Observation

• Registration Number: NCT03469674
• Lead Sponsor: Leiden University Medical Center

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.

Study Timeline

• Study Start: 2016-06-10
• Study First Submitted: 2018-03-08
• Study First Submitted QC: 2018-03-16
• Study First Posted: 2018-03-19
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-10
• Last Update Posted: 2023-10-11
• Primary Completion: 2024-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 550

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Molecular profile based treatment	Observation	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
Molecular profile based treatment	Vaginal brachytherapy	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
Molecular profile based treatment	External beam radiotherapy	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
Vaginal brachytherapy	Vaginal brachytherapy	Adjuvant vaginal brachytherapy (standard treatment)

Primary Outcome Measures

Name	Time	Method
Vaginal recurrence	5 years	Total vaginal recurrence and vaginal recurrence as first failure

Secondary Outcome Measures

Name	Time	Method
Adverse events	5 years	Treatment-related symptoms according to CTCAE v 4.0
Health-related cancer-specific quality of life	5 years	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
Endometrial cancer-related symptoms and quality of life	5 years	Endometrial cancer-related specific symptoms (EORTC EN24 module)- clinically relevant changes on these scales (quite a bit/very much vs no or mild symptoms)
Relapse-free survival	5 years	Relapse-free survival (survival without relapse)
Survival	5 years	Overall survival (all-cause death)
5-year vaginal control including treatment for relapse	5 years	Long-term local control including salvage treatment for local relapse
Pelvic recurrence (total)	5 years	Total pelvic recurrences
Pelvic recurrence as first failure	5 years	Pelvic recurrence as first failure
Distant recurrence (total)	5 years	Total distant recurrences
Distant recurrence as first failure	5 years	Distant recurrence as first failure
Endometrial cancer related health care costs	5 years	All hospital based health care costs used with primary treatment or during followup for treatment of adverse events and/or treatment for relapse

Trial Locations

Locations (31)

CancerTrials Ireland - St James Hospital (SLRON SJH); 🇮🇪 Dublin, Ireland

Academic Medical Center; 🇳🇱 Amsterdam, Netherlands

Haaglanden Medical Center; 🇳🇱 Den Haag, Netherlands

Catharina Hospital; 🇳🇱 Eindhoven, Netherlands

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands

Isala Clinics; 🇳🇱 Zwolle, Netherlands

Medical University, Vienna; 🇦🇹 Vienna, Austria

GINECO group - Institut Goustave Roussy; 🇫🇷 Paris, France

University Hospital Gent; 🇧🇪 Gent, Belgium

Hôpital Européen Georges-Pompidou; 🇫🇷 Paris, France

CEEGOG, General Faculty Hospital and First Faculty of Medicine, Charles University, Prague; 🇨🇿 Praha, Czechia

Hôpital Tenon; 🇫🇷 Paris, France

Universitatsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Universitätsklinikum Schleswig-Holstein, Campus Lübeck; 🇩🇪 Lübeck, Germany

Rotkreuzklinikum München; 🇩🇪 Münich, Germany

University Hospital; 🇩🇪 Tübingen, Germany

NKI / Antoni van Leeuwenhoekhuis; 🇳🇱 Amsterdam, Netherlands

Radiation Therapy Group; 🇳🇱 Arnhem, Netherlands

Radboud University Medical Center; 🇳🇱 Nijmegen, Netherlands

ErasmusMC Cancer Center; 🇳🇱 Rotterdam, Netherlands

Zuidwest Radiotherapy Institute; 🇳🇱 Vlissingen, Netherlands

Radiotherapy Institute Friesland; 🇳🇱 Leeuwarden, Netherlands

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

MAASTRO radiation oncology clinic; 🇳🇱 Maastricht, Netherlands

Verbeeten institute; 🇳🇱 Tilburg, Netherlands

Sankt Gertrauden Krankenhaus; 🇩🇪 Berlin, Germany

Kaiserswerther Diakonie; 🇩🇪 Düsseldorf, Germany

Evang. Kliniken Essen-Mitte; 🇩🇪 Essen, Germany

CancerTrials Ireland - St Luke's Hospital (SLRON SLH); 🇮🇪 Dublin, Ireland

Kantonsspital Frauenklinik Lucerne; 🇨🇭 Lucerne, Switzerland

University Medical Center Utrecht; 🇳🇱 Utrecht, Netherlands