Plain English Summary
Background and study aims
For women with early stage endometrial (womb) cancer, current standard treatment is surgery (removal of the uterus and ovaries) followed by vaginal brachytherapy. Vaginal brachytherapy is a type of radiotherapy where a special applicator is placed in the vagina in which a small pellet of radioactive material is placed to give radiation treatment to the inner part of the vagina. With brachytherapy, the risk of local recurrence (that is, the tumour coming back) is very low and there are very few side effects. However, many women are treated with vaginal brachytherapy, while only few really need this. About 10 women have to be treated to prevent 1 vaginal recurrence. If local recurrence is found, this can be effectively treated at that time. Therefore, treating all women considered to be at risk seems unnecessary. If a better way of predicting which women are likely to suffer a relapse (vaginal recurrence) can be developed then not so many women have to undergo vaginal brachytherapy . This, in turn, will reduce health care costs. In recent years, scientific studies have shown that there are specific alterations in the genes of tumor cells which enable recurrence and the spread of cancer. For endometrial cancer, a better individual risk prediction has been obtained by combining known risk factors with individual alterations in the genes of their tumor. By determining this risk profile on the tumor tissue which has been removed at surgery, a better recommendation can be obtained as to what treatment should be performed, including whether or not vaginal brachytherapy is required
Objectives and design:
In the PORTEC-4a trial, the standard vaginal brachytherapy (standard treatment) will be compared to the use of the individual risk profile to determine adjuvant treatment (favorable: observation; intermediate: vaginal brachytherapy; unfavorable: extermal beam radiotherapy). The aim is to evaluate if the use of the individual risk profile saves many women unnecessary vaginal brachytherapy with similarly high recurrence-free survival and local control, and reduced health costs.
This is a randomised trial, and eligible and consenting women will be randomly assigned (1:2) to vaginal brachytherapy (standard arm) or molecular profile-based recommendations for either observation, vaginal brachytherapy or external beam radiotherapy (investigational arm).
Who can participate?
Women of any age (above 18) who have had surgery (removal of uterus and ovaries) for early stage endometrial cancer.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in group 1 (control group) have
vaginal brachytherapy as usual. Those in group 2 (intervention group) either have no further treatment after surgery, vaginal brachytherapy or external beam radiation therapy, depending upon their molecular profile (that is, the type of alterations in the genes of the tumor cells). All participants are then followed up for at least 5 years to check for recurrence of the tumor, quality of life and any side effects.
What are the possible benefits and risks of participating?
Possible benefits include being spared from further treatment after surgery and have a better understanding what the individual risk of recurrence is.
Where is the study run from?
Lead center is Leiden University Medical Center in the Netherlands. Participating centres are found in all regions of the Netherlands.
When is study starting and how long is it expected to run for?
June 2016 to December 2028
Who is funding the study?
Dutch Cancer Society.
Who is the main contact?
Professor Carien Creutzberg
Study website
Contact information
Type
Scientific
Contact name
Prof Carien Creutzberg
ORCID ID
http://orcid.org/0000-0002-7008-4321
Contact details
Leiden University Medical Centre
Dept of Radiation Oncology
K1-P
Albinusdreef 2
Leiden
2333 ZA
Netherlands
+31.71.526.5120
c.l.creutzberg@lumc.nl
Type
Scientific
Contact name
Dr Anne-Sophie V.M. van den Heerik
ORCID ID
http://orcid.org/0000-0001-6403-0143
Contact details
Leiden University Medical Center
Dept of Radiation Oncology
Albinusdreef 2
Leiden
2333 ZA
Netherlands
+31 (0)71 526 5539
a.v.m.van_den_heerik@lumc.nl
Additional identifiers
EudraCT/CTIS number
IRAS number
ClinicalTrials.gov number
NCT03469674
Protocol/serial number
UL2011-5336; P16.054; NL56828.058.16
Study information
Scientific title
PORTEC-4a: Randomised Phase III Trial of molecular profile-based versus standard recommendations for adjuvant radiotherapy for women with early stage endometrial cancer
Acronym
PORTEC-4a
Study hypothesis
Molecular risk profile-based recommendations for no additional treatment (55%), vaginal brachytherapy (40%) or external beam radiotherapy (5%) will lead to similar vaginal control for women with early stage endometrial cancer with high-intermediate risk features, while sparing about 50% of these women vaginal brachytherapy and reducing health care usage.
Ethics approval(s)
Committee for Medical Ethics, Leiden University Medical Center, Leiden, The Netherlands, 10/05/2016, ref: P16.054
Study design
Randomised multicenter phase III trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
https://msbi.nl/promise/LinkClick.aspx?fileticket=IYQIkIT4IHw%3d&tabid=125&portalid=0&mid=581
Condition
Endometrial cancer
Intervention
Participants are randomly allocated to one of two arms:
1. Standard arm:
Vaginal brachytherapy (3 short outpatient internal radiation treatments over 2 weeks to the vaginal cuff), based on PORTEC-2 trial.
2. Investigational arm:
Based on the molecular profile, either no further treatment after surgery (for favourable profile), or vaginal brachytherapy (as above, for intermediate profile) or external beam radiation therapy (5 weeks of daily out-patient external radiation treatments to the pelvic area, for unfavourable profile).
After completion of patient recruitment, follow-up will continue until the time of final analysis is reached and until at least 5 years after inclusion of each patient.
Intervention type
Other
Primary outcome measure
Vaginal recurrence, measured during each follow-up visit by vaginal inspection and pelvic examinations (3 monthly first 2 years, 6 monthly until 5th year) and confirmation by histology in case of suspected recurrence
Secondary outcome measures
1. Recurrence-free survival - regular follow-up visits (3 monthly first 2 years, 6 monthly until 5th year) with history focused on symptoms and side effects and pelvic examination; further evaluation in case of suspected recurrence locally or at distant sites by (PET)-CT and/or MRi scanning and histological confirmation. In case of death, information on date and cause of death are recorded
2. 5-year vaginal control - local recurrence free at 5 years either without any evidence of recurrence or after treatment for vaginal recurrence
3. Quality of life- Patients receive a QoL questionnaire consisting of EORTC QLQ-C30 and EN24 at baseline (after surgery, before study treatment or observation), at 6 weeks after randomisation, and at 6, 12, 18, 24, 36 and 60 months after randomisation
4. Side effects- Regular follow-up visits (3 monthly first 2 years, 6 monthly until 5th year) with history focused on symptoms and side effects – recording of adverse events according to CTCAEv 4.0
5. Health care costs - EC-related healthcare costs will include the costs of the randomised care and care associated with (serious) adverse events. Healthcare use over the follow-up period will be converted to costs using standard prices, discounted over time. Costs will be evaluated at each follow-up and at recurrence by recording hospital admissions, surgeries, etc over the past follow-up period
Overall study start date
01/06/2016
Overall study end date
31/12/2028
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Histologically confirmed endometrioid type endometrial carcinoma, FIGO 2009 stage I, with one of the following combinations of stage, grade, age, and 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
WHO-performance status 0-2
Written informed consent
Participant type(s)
Patient
Age group
Adult
Sex
Female
Target number of participants
550
Participant exclusion criteria
1. Any other stage and type of endometrial carcinoma
2, Histological types papillary serous carcinoma or clear cell carcinoma (at least 10% if mixed type)
3. Undifferentiated or neuroendocrine carcinoma
4. Uterine sarcoma (including carcinosarcoma)
5. Previous malignancy (except for non-melanomatous skin cancer) < 5 yrs
6. Previous pelvic radiotherapy
7. Interval between the operation and start of radiotherapy exceeding 8 weeks
Updated 17/08/2021:
7. Expected interval between the operation and start of radiotherapy exceeding 8 weeks
Recruitment start date
01/06/2016
Recruitment end date
24/12/2021
Locations
Countries of recruitment
Austria, Belgium, Czech Republic, France, Germany, Ireland, Netherlands, Switzerland
Study participating centre
Leiden University Medical Center (lead center)
2333 ZA Leiden
Netherlands
Study participating centre
Academic Medical Center
Amsterdam
-
Netherlands
Study participating centre
Catharina Hospital
Eindhoven
-
Netherlands
Study participating centre
Erasmus Medical Center
Rotterdam
-
Netherlands
Study participating centre
Institute Verbeeten
Tilburg
-
Netherlands
Study participating centre
Isala Clinics
Zwolle
-
Netherlands
Study participating centre
Maastricht Radiation Oncology Clinic
Maastricht
-
Netherlands
Study participating centre
Medical Centre Haaglanden
Den Haag
-
Netherlands
Study participating centre
NKI/Antoni v. Leeuwenhoekhuis (The Netherlands Cancer Institute)
Amsterdam
-
Netherlands
Study participating centre
Radiotherapy Group, Arnhem
Arnhem
-
Netherlands
Study participating centre
Radiotherapy Institute Friesland, Leeuwarden
Leeuwarden
-
Netherlands
Study participating centre
University Medical Center Groningen
Groningen
-
Netherlands
Study participating centre
University Medical Center Radboud
Nijmegen
-
Netherlands
Study participating centre
University Medical Center Utrecht
Utrecht
-
Netherlands
Study participating centre
Zuidwest Radiotherapy Institute
Vlissingen
-
Netherlands
Study participating centre
University Hospital Gent
Corneel Heymanslaan 10
Gent
9000
Belgium
Study participating centre
University Hospital Tubingen
Hoppe-Seyler-Straße 3
Tübingen
72076
Germany
Study participating centre
Rotkreuzklinikum München
Rotkreuzpl. 8
München
80634
Germany
Study participating centre
Kliniken Essen-Mitte
Henricistraße 92
Essen
45136
Germany
Study participating centre
Universitätsklinikum Schleswig-Holstein
Campus Lübeck
Ratzeburger Allee 160
Lübeck
23562
Germany
Study participating centre
Kaiserswerther Diakonie Düsseldorf
Kreuzbergstraße 79
Düsseldorf
40489
Germany
Study participating centre
Universitatsklinikum Heidelberg
Im Neuenheimer Feld 672
Heidelberg
69120
Germany
Study participating centre
Sankt Gertrauden Krankenhaus Berlin
Paretzer Straße 12
Berlin
10713
Germany
Study participating centre
Kantonsspital Frauenklinik Lucerne
Spitalstrasse
PO Box 6000
Luzern
16
Switzerland
Study participating centre
Saint Luke’s Radiation Oncology Network (SLRON), Dublin
Oakland Drive
Highfield Road
Dublin
6
Ireland
Study participating centre
St James’s Hospital (SJH), Dublin
James Street
Dublin
8
Ireland
Study participating centre
University Hospital Prague
U Nemocnice 499/2
Prague
128 08
Czech Republic
Study participating centre
Institut Gustave-Roussy, Paris
114, rue Édouard-Vaillant
Villejuif Cedex
94805
France
Study participating centre
Hôpital Européen Georges-Pompidou, Paris
20 Rue Leblanc
Paris
75015
France
Study participating centre
Hôpital Tenon, Paris
4 Rue de la Chine
Paris
75020
France
Study participating centre
Medical University, Vienna
Spitalgasse 23
Wien
1090
Austria
Sponsor information
Organisation
Leiden University Medical Center
Sponsor details
Albinusdreef 2
Leiden
2333 ZA
Netherlands
Sponsor type
Hospital/treatment centre
Website
ROR
Funders
Funder type
Charity
Funder name
KWF Kankerbestrijding
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
To be confirmed at later date
Protocol is available online. Publication of the trial results after we have completed the trial.
We may publish the trial background and design in a Dutch oncology and possibly later on also in the UK when international participation is getting started.
Intention to publish date
31/12/2024
Individual participant data (IPD) sharing plan
After publication of the full results (including long-term results) the de-identified data will be available for relevant scientific studies, upon request and submission of a research proposal, and after evaluation of the PORTEC-group.
IPD sharing plan summary
Available on request
Study outputs
Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
---|---|---|---|---|---|
Results article | results | 01/10/2018 | Yes | No | |
Participant information sheet | Short patient information in English | 17/08/2021 | No | Yes | |
Participant information sheet | v2.2 | 09/04/2016 | 17/08/2021 | No | Yes |
Participant information sheet | v2.5.1 | 26/06/2020 | 17/08/2021 | No | Yes |
Protocol article | 12/10/2020 | 17/08/2021 | Yes | No | |
Results article | Brachytherapy quality assurance | 05/11/2020 | 17/08/2021 | Yes | No |