Hypofractionated Radiotherapy as Primary Therapy for Prostate Cancer

NCT01921803 | Completed Phase 2

• 1 other identifier: 2013/380
• Study Type: interventional
• Target: 346
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (2)

• change in quality of life

  from start to 24 months after radiotherapy

• cost effectiveness

  24 months after radiotherapy

Study Arms (2)

Arm 1

EXPERIMENTAL

16 fractions à rato of 4 fractions a week over 4 weeks

Radiation: hypofractionation

Arm 2

EXPERIMENTAL

25 fractions à rato of 5 fractions a week over 5 weeks

Radiation: hypofractionation

Interventions

hypofractionation RADIATION

Arm 1; Arm 2

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients with T1-4 N0 M0 prostate cancer

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital, Ghent: lead

Study Sites (1)

Ghent University Hospital

Ghent, 9000, Belgium

Location

Related Publications (1)

• 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.

  PMID: 29485064 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radiation Dose Hypofractionation

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics

Study Officials

• Valerie Fonteyne

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2013
• First Posted: August 13, 2013
• Study Start: August 1, 2013
• Primary Completion: July 14, 2020
• Study Completion: July 14, 2020
• Last Updated: December 22, 2022

Record last verified: 2022-12

Locations

BE (1)