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

Study Overview
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Brief Summary
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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.

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

Conditions
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Carcinoma of the Prostate

Intervention / Treatment
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* Radiation: HDR 2 Fraction
* Radiation: HDR 1 Fraction


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HDR 2 fractions<br>HDR brachytherapy of 27 Gy delivered in 2 fractions one week apart | Radiation: HDR 2 Fraction<br>* High dose-rate brachytherapy using real-time intra-operative transrectal ultrasound guidance. Patients will receive 27 Gy as a minimal Clinical Target Volume (CTV) dose delivered as two fractions of 13.5 Gy 7-13 days apart. The CTV is the ultrasound defined prostate with a 0-2 mm margin.<br>|
| Experimental: HDR 1 fraction<br>HDR brachytherapy of 19 Gy delivered in a single fraction | Radiation: HDR 1 Fraction<br>* High Dose-Rate Brachytherapy delivered in same manner as Arm 1, but to a prescribed CTV minimal dose of 19 Gy in a single fraction<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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) | 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 | 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 | 5 years | 
| Erectile function | To determine changes in erectile function in both study arms assessed using the International Index of Erectile Function (IIEF) scale | 5 year | 
| Associations between dosimetric parameters and toxicity/EPIC domains | To explore association between dosimetric parameters and toxicity/EPIC domain change | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HDR, monotherapy, low, intermediate, prostate cancer