A Phase II Trial of High Dose-Rate Brachytherapy as Monotherapy in Low and Intermediate Risk Prostate Cancer

Sunnybrook Health Sciences Centre174 enrolled

Overview

A single high dose rate brachytherapy (HDR) treatment combined with a short course of external beam radiotherapy (EBRT) is a highly effective and well tolerated treatment for men with intermediate risk prostate cancer. High cancer control rates have also been reported with HDR used on its own, without the EBRT. The challenge has been to determine what HDR dose to use with a move towards one or two fractions by several investigators. These schedules are reported to be well tolerated in the short term, but with little long term data. The objective of this study is to investigate HDR monotherapy given as either one fraction of 19 Gy or two fractions of 13.5 Gy in a randomized phase II clinical trial. The primary endpoint is patient reported toxicity and health related quality of life at 1 year, and efficacy data will be also be analyzed. Sample size for the study is 174 patients, which we expect to accrue within 18 months.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

174

Conditions

Carcinoma of the Prostate

Interventions

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * histologically confirmed diagnosis of adenocarcinoma of the prostate * low and intermediate risk disease defined as either Gleason 6 or Gleason 7 and PSA \< 20ng/mL. PSA to be drawn within 60 days of registration * prostate volume \< 60 cc as determined by ultrasound, CT or MRI * willing to give informed consent ot participate in this clinical trial * able and willing to complete Expanded Prostate Index Composite (EPIC) questionnaire Exclusion Criteria: * documented nodal or distant metastases * previous pelvic radiotherapy * previous trans-urethral resection of prostate, previous prostatectomy or Highly Focused Ultrasound (HIFU) * use of androgen deprivation therapy. Use of 5-alpha reductase inhibitors is permitted * poor baseline urinary function defined as radiotherapy eg. connective tissue disease or inflammatory bowel disease * significant medical co-morbidity rendering patient unsuitable for general anaesthetic

Outcomes

Primary Outcomes

Health related quality of life (QoL)

To demonstrate that health related QoL at 1 year in the urinary and bowel domains of the Expanded Prostate Index Composite (EPIC) for at least one HDR monotherapy arm is not worse than that following current standard treatment with single fraction HDR combined with supplemental external beam radiotherapy.

Time frame: 1 year

Secondary Outcomes

GU and GI toxicities

To determine genito-urinary (GU) and gastro-intestinal (GI) toxicities in both study arms according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0

Time frame: baseline, 6 weeks post treament, 3mths, 6mths, 6 monthly for the first 3 years, annually up to 5 years

Urinary Symptoms

To determine changes in urinary symptoms in both study arms as determined by the International Prostate Symptom Score (IPSS)

Time frame: baseline, 6 weeks post treatment, 3 mths, 6 mths, 6-monthly for the first 3 years, annually until 5 years

Serum PSA changes

To determine changes in serum prostate-specific antigen (PSA) in both arms

Time frame: baseline, 6 weeks post treatment, 3 mths, 6 mths, 6-monthly up to 3 years, annually until 5 years

Biochemical failure and disease free survival rates

To determine PSA failure and disease free survival rates in both study arms

Time frame: 5 years

Erectile function

To determine changes in erectile function in both study arms assessed using the International Index of Erectile Function (IIEF) scale

Time frame: 5 year

Associations between dosimetric parameters and toxicity/EPIC domains

To explore association between dosimetric parameters and toxicity/EPIC domain change