Hypofractionated Radiotherapy as Primary Therapy for Prostate Cancer (Hypofraction)

Hypofractionated Radiotherapy as Primary Therapy for Prostate Cancer: Randomised Trial Comparing Toxicity Between 2 Different Hypofractionated Schedules

External beam radiotherapy (RT) is one of the standard curative treatment options for patients with prostate cancer (PC). Several randomised trials have shown excellent long-term biochemical outcome with higher radiation doses. Nowadays, RT for PC commonly consists of delivering 74-80 Gy in 2 Gy fractions, resulting in an overall treatment time of 7-8 weeks. The sensitivity of different tissues to fractionation changes can be quantified through the α/β ratio in the linear-quadratic model. Dose-response analysis of PC patients treated with both external beam RT and brachytherapy has led to the hypothesis that the α/β ratio of PC is lower than for most other tumors and approaches a value characteristic of late responding tissues. Values between 1.2 and 3.9 Gy have been calculated. If the α/β ratio of PC is indeed low, then hypofractionating RT treatments can theoretically maintain high bioequivalent tumor doses, shorten overall treatment time and decrease late toxicities.The advantages in terms of patient convenience and treatment cost are obvious. There is level I evidence that shows that hypofractionated radiotherapy schedules have at least equivalent biochemical outcome with only a small increase in acute but not late toxicity when compared to conventional fractionation RT schedules.

Results on different hypofractionation schedules have been reported, however the optimal hypofractionation is not clear so far. In this randomised trial we would like to compare 2 different radiotherapyschedules: 16 fractions à rato of 4 fractions a week versus 25 fractions à rato of 5 fractions a week. The incidence on acute toxicity and early late toxicity (i.e. within 2 year post radiotherapy) and the impact on quality of life will be registrated and compared. The study will be performed in 2 stages. For stage 1, sample size was calculated to rule out an upper limit of 40% of patients with RTOG grade 2 or worse bowel (GI) complications with an expected rate of 25%, based on a one-stage Fleming-A'Hern design. A power of 83.0% (alpha level 0.038 one-sided) was obtained when including 72 patients per group (144 patients in total). If 22 or more patients out of 72 had grade 2 or worse GI complications, then the study arm was to be rejected. To allow for a dropout of 10%, 160 patients were included in stage 1. Sample size for stage 2 was calculated analogously allowing ruling out an upper limit of 35% of patients with RTOG grade 2 or worse GI complications with an expected rate of 25%. When including 155 patients per group (310 in total) a power of 85.7% (alpha level 0.049 one-sided) was obtained. If 45 or more patients out of 155 had grade 2 or worse GI complications, then the study arm was to be rejected. The sample size for stage 1 and stage 2 combined was set at 346 (173 per group), with a 10% allowance for dropout.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: hypofractionation

• Study Type: Interventional
• Enrollment (Actual): 346
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Ghent University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• patients with T1-4 N0 M0 prostate cancer

Exclusion Criteria:

• other no skin cancer diagnosed within 5 years prior to enrolment
• no informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; 16 fractions à rato of 4 fractions a week over 4 weeks	Radiation: hypofractionation
Experimental: Arm 2; 25 fractions à rato of 5 fractions a week over 5 weeks	Radiation: hypofractionation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
acute and early late toxicity	A maximal incidence of 40% of Grade 2 gastro-intestinal (GI) toxicity is allowed. Evaluation of difference in grade 2 and 3 GI toxicity.	pre radiotherapy
acute and early late toxicity		1 month after radiotherapy
acute and early late toxicity		3 months after radiotherapy
acute and early late toxicity		6 months after radiotherapy
acute and early late toxicity		9 months after radiotherapy
acute and early late toxicity		12 months after radiotherapy
acute and early late toxicity		18 months radiotherapy
acute and early late toxicity		24 months radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in quality of life	EORTC QLQ-C30 and EORTC QLQ-PR25; EQ-5D-5L	from start to 24 months after radiotherapy
cost effectiveness		24 months after radiotherapy

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Valérie Fonteyne, University Hospital, Ghent

Publications and helpful links

General Publications

• Fonteyne V, Sarrazyn C, Swimberghe M, De Meerleer G, Rammant E, Vanderstraeten B, Vanpachtenbeke F, Lumen N, Decaestecker K, Colman R, Villeirs G, Ost P. 4 Weeks Versus 5 Weeks of Hypofractionated High-dose Radiation Therapy as Primary Therapy for Prostate Cancer: Interim Safety Analysis of a Randomized Phase 3 Trial. Int J Radiat Oncol Biol Phys. 2018 Mar 15;100(4):866-870. doi: 10.1016/j.ijrobp.2017.12.016. Epub 2017 Dec 19.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2013
• Primary Completion (Actual): July 14, 2020
• Study Completion (Actual): July 14, 2020

Study Registration Dates

• First Submitted: July 30, 2013
• First Submitted That Met QC Criteria: August 9, 2013
• First Posted (Estimate): August 13, 2013

Study Record Updates

• Last Update Posted (Actual): December 22, 2022
• Last Update Submitted That Met QC Criteria: December 21, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 2013/380