Phase II study of extreme hypofractionated radiotherapy for localized prostate cancer

ISRCTN	ISRCTN19419439
DOI	https://doi.org/10.1186/ISRCTN19419439
Secondary identifying numbers	GRS 903/A/14

Submission date: 11/07/2018
Registration date: 23/07/2018
Last edited: 06/08/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Radiotherapy is a treatment where radiation is used to kill cancer cells and can be used to treat prostate cancer. The effectiveness of radiotherapy for the treatment of prostate cancer improves when high doses are delivered to the prostate, especially in aggressive, localised prostate cancer. The standard method of radiotherapy is to deliver small daily doses over the course of 8 weeks; however, as the dose increases over this time, so do the side effects.
Recent evidence shows that, instead of small doses over a longer time period, higher daily doses over a few weeks, mean that higher doses of radiotherapy can be given without increasing the side effects of the treatment, along with improving rates of curing the cancer. This has been shown in patients with low-risk and some patients with intermediate-risk prostate cancer.
We aim to look at whether similar results can be achieved for patients with intermediate-risk and high-risk prostate cancer through 8 days of high dose radiotherapy.

Who can participate?
Localised prostate cancer patients

What does the study involve?
All participants receive high dose radiotherapy on 8 days across 3 weeks, along with traditional androgen deprivation therapy. Additionally, patients will be regularly tested for toxicity, PSA levels and metastasis for 10 years following the study.

What are the possible benefits and risks of participating?
The benefits to participants of taking part include potential curing of their cancer with reduced side effects, along with an improved quality of life. Additionally, the treatment scheme is short, which is more convenient for patients. A possible risk of taking part is unexpected toxicity/side effects.

Where is the study run from?
Salamanca University Hospital, Spain

When is the study starting and how long is it expected to run for?
January 2012 to December 2022

Who is funding the study?
Castille-Leon Autonomous Community public health system (Spain)

Who is the main contact?
Dr Victor Macias-Hernandez (radiation oncologist/clinical oncologist)
victormaciash@gmail.com

Contact information

Dr VICTOR MACIAS-HERNANDEZ
Scientific

Paseo de San Vicente
Salamanca
37007
Spain

ORCID ID	0000-0003-2904-5715
Phone	+34687481166
Email	victormaciash@gmail.com

Study information

Study design	Interventional prospective single-centre non-randomised study
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use contact details to request a participant information sheet
Scientific title	Phase II single-centre trial of Extreme Hypofractionated RAdiotherapy for low, intermediate and high-risk localised Prostate cancer
Study acronym	EHRAP
Study objectives	Late toxicity, quality of life and biochemical-free survival outcomes after extreme hypofractionated radiotherapy for localized prostate cancer are not inferior to normofractionated or moderate hypofractionated radiotherapy
Ethics approval(s)	The Spanish Agency of Medicines and Medical Devices (AEMPS) , 29/01/2013, PI 120413
Health condition(s) or problem(s) studied	Low, intermediate and highrisk prostate cancer
Intervention	Participants with low, intermediate and high risk prostate cancer received extreme hypofractionated radiotherapy using helical tomotherapy, with online guided MVCT and an endorectal balloon. This radiotherapy delivered 8 fractions of 5.65 Gy radiation over 3 weeks. Additionally, participants received androgen deprivation therapy as usually prescribed in normal standard - for those with intermediate-risk prostate cancer, this consisted of one 6 month LHRH analogue and 1 month bicalutamide; for those with high-risk prostate cancer, this consisted of 2-3 years of 6 month LHRH analogue and 1 month bicalutamide. Patients will be interviewed at least 2, 6, 12, 18, 24, 30, 36, 48 and 60 months after radiotherapy and every year afterwards up to 10 years, and will be asked about symptoms, along with undergoing urine and blood tests and quality of life questionnaires. At each visit, the following will be tested: 1. Urinary and intestinal toxicity, if any, according to CTCAE scale 2. Health-related quality of life 3. PSA levels (from blood tests performed a few weeks before each visit). If a PSA relapse is found, a rectal examination will be performed to detect a local clinical relapse. 4. Metastases (examined through CT scans and bone scans)
Intervention type	Procedure/Surgery
Primary outcome measure	The following are measured at the baseline and 2, 6, 12, 18, 24, 30, 36, 48 and 60 months after radiotherapy and every year afterwards: 1. Urinal and intestinal toxicities measured using CTCAE (Common Toxicity Criteria Adverse Effects) scale 2. Health-related quality of life measured using EPIC-26 (Expanded Prostate Cancer Index Composite short form)
Secondary outcome measures	1. PSA relapse free survival (nadir+2 ng/ml) is measured using total PSA levels (determined through blood test performed a few weeks before visit) measured at the baseline and 2, 6, 12, 18, 24, 30, 36, 48 and 60 months after radiotherapy and every year afterwards 2. Metastases-free survival is measured using a CT scan and bone scan, evaluated at the baseline and every 6 months only after a biochemical relapse is diagnosed (PSA > 2 ng + nadir, ASTRO definition)
Overall study start date	01/01/2012
Completion date	31/07/2023

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Male
Target number of participants	120
Key inclusion criteria	1. cT1-T3 N0 M0 prostate cancer 2. International Prostate Symptoms Score < 21 3. No acute urinary retention or urethral surgery in the last 6 months 4. Aged 18 years or older 5. Signed specific informant consent form
Key exclusion criteria	1. Hip prosthesis 2. Contraindication for radical radiotherapy such as active inflamatory bowel disease, previous pelvic radiotherapy 3. Intense low urinary tract symptoms, IPSS > 20 4. Inability to understand and appreciate the nature and consequences of health decisions
Date of first enrolment	01/06/2013
Date of final enrolment	31/12/2017

Locations

Countries of recruitment

Spain

Study participating centre

Complejo Asistencial Universitario de Salamanca (Salamanca University Hospital)

Paseo de San Vicente, 137
Salamanca
37007
Spain

Sponsor information

Hospital Universitario de Salamanca (Salamanca University Hospital)
Hospital/treatment centre

Paseo de San Vicente
Salamanca
37007
Spain

Phone	+34923291200
Email	vamacias@saludcastillayleon.es
Website	https://www.saludcastillayleon.es/CASalamanca/es
"ROR"	https://ror.org/0131vfw26

Funders

Funder type

Not defined

Investigator initiated and funded

No information available

Spanish Autonomous Comunity grant code GRS 903/A/14, from SACYL (Castille and Leon Public Health Service)

No information available

Results and Publications

Intention to publish date	01/06/2019
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
Publication and dissemination plan	Accepted oral communication at American Society of Radiation Oncology annual meeting on october 2018. To send to a peer-review journal in 2019. Updated results with longer follow-up to be published in 2021.
IPD sharing plan	The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	early toxicity results	26/11/2014		Yes	No
Results article	results	01/11/2018		Yes	No
Results article		15/10/2019	06/08/2024	Yes	No

Editorial Notes

06/08/2024: Publication reference added.
05/12/2018: Publication reference added.