LDR vs. HDR Brachytherapy for Prostate Cancer

Study Overview
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Brief Summary
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H17-02904 is a randomized comparison of low dose rate vs. high dose rate prostate brachytherapy for favorable and intermediate risk prostate cancer suitable for brachytherapy as monotherapy. This is a continuation with expanded accrual of the randomized Pilot study H15-02103

Detailed Description
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Men suitable for prostate brachytherapy as monotherapy will undergo multiparametric Magnetic Resonance Imaging for staging and identification of a dominant lesion and will be randomly selected for either a single low dose rate permanent seed implant or 2 fractions of high dose rate brachytherapy. Using image registration techniques, dominant lesions will be biopsied under anesthesia at the start of the brachytherapy procedure. Biopsies will reviewed for tumor Gleason score and sent for Cell Cycle Progression testing (Prolaris). Patients receiving high dose rate brachytherapy will also have biopsies between the 2 fractions to assess tumor changes induced from the first fraction. Post implant quality assurance will determine the dose to the dominant lesions and compare these between the 2 types of brachytherapy. Post implant symptoms will be tracked for severity and time course.

Official Title
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A Phase III Randomized Study of Low Dose Rate Compared to High Dose Rate Prostate Brachytherapy for Favorable Risk and Low Tier Intermediate Risk Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: Low dose rate prostate brachytherapy
* Radiation: High dose rate prostate brachytherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Favorable risk and low-tier intermediate-risk prostate cancer with estimated life expectancy of at least 10 years. Clinical stage T1c-T2b, PSA < 20, Gleason < 8 ECOG 0-1 Low tier intermediate-risk prostate cancer is defined by a single NCCN intermediate risk factor Extensive favorable-risk disease is defined as: clinical stage T1c-T2a PSA < 10 Gleason 6 ≥ 50% of biopsy cores containing cancer PSA density > 0.2 ng/cc Selected intermediate risk patients not defined above - T1c/T2a - PSA < 10 -Gleason 4+3 -< 33% of cores involved -Max tumor length in any core 10 mm No androgen deprivation therapy (ADT) Prostate volume by TRUS ≤ 60 cc. Not eligible for, or accepting of, active surveillance according to NCCN guidelines. Signed study specific informed consent. Exclusion Criteria: Prior radical surgery for carcinoma of the prostate, Prior pelvic radiation Prior chemotherapy for prostate cancer, Prior TURP or cryosurgery of the prostate Claustrophobic or unable to undergo MRI

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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 |
| --- | --- |
| Active Comparator: Low dose rate brachytherapy<br>Device: Radiation. Low dose rate prostate brachytherapy is delivered under anesthesia in a single 1.5-2 hour procedure as an out-patient. The men return 4 weeks later for detailed imaging to assess implant quality. | Radiation: Low dose rate prostate brachytherapy<br>* Permanent implantation of radioactive Iodine-125 seeds under anesthesia with ultrasound guidance<br>* Other names: permanent seed implant;|
| Experimental: High dose rate brachytherapy<br>Device: Radiation. High dose rate prostate brachytherapy is delivered in 2 procedures, 2 weeks apart, also under anesthesia, but no follow-up imaging visit is required. HDR brachytherapy is also accomplished as an out-patient. | Radiation: High dose rate prostate brachytherapy<br>* Temporary implantation of radioactive material into the prostate in the form of a stepping source of Iridium 192 that travels through 16-18 needles or catheters strategically placed through the prostate<br>* Other names: HDR brachytherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in Quality of Life in the urinary domain between LDR and HDR brachytherapy. | The urinary domain of the EPIC prostate cancer specific QOL questionnaire will be assessed. | 0-36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life in the bowel and sexual domains | The EPIC score in the bowel and sexual domains will be evaluated at baseline, 1, 3, 6, 12, 24 and 36 months | 0-36 months | 
| Time to return to baseline +/- 3 points for the International Prostate Symptom Score | The IPS Score will be assessed at baseline, 1, 3, 6, 12, 24 and 36 months | 0-36 months | 
| Acute and long term toxicity | Acute and long-term toxicity will be graded using the Common Terminology Criteria for Adverse Events (CTCAE V4) at each follow up time point | [Time Frame: 0-10 years] | 
| Biochemical Outcome | PSA will be recorded every 6 months to 5 years and then annually to 10 years | 5-10 years | 
| Histologic Outcome | Prostate re-biopsy will be performed at 36 months to assess the local efficacy of treatment | 3 years | 
| Cell cycle progression score | For those patients consenting to targeted biopsies under anesthesia at the start of their brachytherapy procedure (separate optional consent) MRI-TRUS fusion accuracy will be verified by targeted biopsies and Biopsy material will be sent for genetic testing to determine Cell cycle Progression scores for both arms of the trial to ultimately correlate with outcome. | 1 month to 10 years | 
| Tumor oxygenation and cell cycle distribution | For patients receiving 2 fractions of high dose rate brachytherapy, biopsy between the 2 fractions will assess radiosensitivity by evaluating changes in oxygenation and cell cycle distribution between the 2 fractions, for ultimate correlation with efficacy | 1 month to 10 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brachytherapy, Quality of life, High dose rate vs. low dose rate, Intermediate risk group