Condition category
Cancer
Date applied
03/06/2016
Date assigned
24/06/2016
Last edited
28/06/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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 June 2025

Who is funding the study?
Dutch Cancer Society.

Who is the main contact?
Professor Carien Creutzberg

Trial website

www.msbi.nl/portec4

Contact information

Type

Scientific

Primary contact

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

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

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

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

https://www.msbi.nl/promise/Portals/0/Users/027/27/27/Patienteninformatie_PORTEC4a_V2.2_compleet.pdf?ver=2016-05-31-203513-813 (in Dutch)

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

Phase

Drug names

Primary outcome measures

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 trial start date

01/06/2016

Overall trial end date

01/06/2025

Reason abandoned

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

Patient

Age group

Adult

Gender

Female

Target number of participants

500

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

Recruitment start date

01/06/2016

Recruitment end date

31/12/2020

Locations

Countries of recruitment

Australia, Netherlands, New Zealand, United Kingdom

Trial participating centre

Leiden University Medical Center (lead center)
2333 ZA Leiden
Netherlands

Trial participating centre

Academic Medical Center
Amsterdam
-
Netherlands

Trial participating centre

Catharina Hospital
Eindhoven
-
Netherlands

Trial participating centre

Erasmus Medical Center
Rotterdam
-
Netherlands

Trial participating centre

Institute Verbeeten
Tilburg
-
Netherlands

Trial participating centre

Isala Clinics
Zwolle
-
Netherlands

Trial participating centre

Maastricht Radiation Oncology Clinic
Maastricht
-
Netherlands

Trial participating centre

Medical Spectrum Twente
Enschede
-
Netherlands

Trial participating centre

Medical Centre Haaglanden
Den Haag
-
Netherlands

Trial participating centre

NKI/Antoni v. Leeuwenhoekhuis (The Netherlands Cancer Institute)
Amsterdam
-
Netherlands

Trial participating centre

Radiotherapy Group, Arnhem
Arnhem
-
Netherlands

Trial participating centre

Radiotherapy Group, Deventer
Deventer
-
Netherlands

Trial participating centre

Radiotherapy Institute Friesland, Leeuwarden
Leeuwarden
-
Netherlands

Trial participating centre

University Medical Center Groningen
Groningen
-
Netherlands

Trial participating centre

University Medical Center Radboud
Nijmegen
-
Netherlands

Trial participating centre

University Medical Center Utrecht
Utrecht
-
Netherlands

Trial participating centre

Zuidwest Radiotherapy Institute
Vlissingen
-
Netherlands

Sponsor information

Organisation

Leiden University Medical Center

Sponsor details

Albinusdreef 2
Leiden
2333 ZA
Netherlands

Sponsor type

Hospital/treatment centre

Website

www.lumc.nl

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 on line. 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 UK when international participation is getting started

Intention to publish date

31/12/2021

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

28/06/2016: Internal review