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

Endometrial Cancer Stage I Clinical Trial

— PORTEC-4a  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03469674
• Other study ID #: P16.054
• Secondary ID: UL2011-5336ISRCT
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 10, 2016
• Est. completion date: December 31, 2028

Study information

• Verified date: October 2023
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 external beam radiotherapy based on a favourable, intermediate or unfavourable profile as compared to standard adjuvant vaginal brachytherapy.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 550
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Endometrial Cancer Stage I
• Endometrial Cancer Stage II
• Endometrial Neoplasms

Intervention

Radiation:
• Vaginal brachytherapy
Internal radiation of the vaginal vault using a vaginal cylinder, 21 Gy in 3 out-patient sessions over 2 weeks
• External beam radiotherapy
External beam pelvic radiotherapy on a linear accelerator, 48.6 Gy in 27 out-patients sessions over 5.5 weeks

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

Locations

Country	Name	City	State
Austria	Medical University, Vienna	Vienna
Belgium	University Hospital Gent	Gent
Czechia	CEEGOG, General Faculty Hospital and First Faculty of Medicine, Charles University, Prague	Praha
France	GINECO group - Institut Goustave Roussy	Paris
France	Hôpital Européen Georges-Pompidou	Paris
France	Hôpital Tenon	Paris
Germany	Sankt Gertrauden Krankenhaus	Berlin
Germany	Kaiserswerther Diakonie	Düsseldorf
Germany	Evang. Kliniken Essen-Mitte	Essen
Germany	Universitatsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Schleswig-Holstein, Campus Lübeck	Lübeck
Germany	Rotkreuzklinikum München	Münich
Germany	University Hospital	Tübingen
Ireland	CancerTrials Ireland - St James Hospital (SLRON SJH)	Dublin
Ireland	CancerTrials Ireland - St Luke's Hospital (SLRON SLH)	Dublin
Netherlands	Academic Medical Center	Amsterdam
Netherlands	NKI / Antoni van Leeuwenhoekhuis	Amsterdam
Netherlands	Radiation Therapy Group	Arnhem
Netherlands	Haaglanden Medical Center	Den Haag
Netherlands	Catharina Hospital	Eindhoven
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Radiotherapy Institute Friesland	Leeuwarden
Netherlands	Leiden University Medical Center	Leiden
Netherlands	MAASTRO radiation oncology clinic	Maastricht
Netherlands	Radboud University Medical Center	Nijmegen
Netherlands	ErasmusMC Cancer Center	Rotterdam
Netherlands	Verbeeten institute	Tilburg
Netherlands	University Medical Center Utrecht	Utrecht
Netherlands	Zuidwest Radiotherapy Institute	Vlissingen
Netherlands	Isala Clinics	Zwolle
Switzerland	Kantonsspital Frauenklinik Lucerne	Lucerne

Sponsors (3)

Lead Sponsor	Collaborator
Leiden University Medical Center	Comprehensive Cancer Centre The Netherlands, Dutch Cancer Society

Countries where clinical trial is conducted

Austria,  Belgium,  Czechia,  France,  Germany,  Ireland,  Netherlands,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Recurrence (vaginal and total) per risk profile	Vaginal, pelvic and distant relapse split by risk profile and compared between the 2 arms	5 years
Primary	Vaginal recurrence	Total vaginal recurrence and vaginal recurrence as first failure	5 years
Secondary	Adverse events	Treatment-related symptoms according to CTCAE v 4.0	5 years
Secondary	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	5 years
Secondary	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)	5 years
Secondary	Relapse-free survival	Relapse-free survival (survival without relapse)	5 years
Secondary	Survival	Overall survival (all-cause death)	5 years
Secondary	5-year vaginal control including treatment for relapse	Long-term local control including salvage treatment for local relapse	5 years
Secondary	Pelvic recurrence (total)	Total pelvic recurrences	5 years
Secondary	Pelvic recurrence as first failure	Pelvic recurrence as first failure	5 years
Secondary	Distant recurrence (total)	Total distant recurrences	5 years
Secondary	Distant recurrence as first failure	Distant recurrence as first failure	5 years
Secondary	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	5 years

External Links

•   Study website