Comparison of HDR vs. LDR Brachytherapy as Monotherapy for Intermediate Risk Prostate Cancer

May 19, 2023 updated by: Juanita Crook, British Columbia Cancer Agency

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

This study will offer men with intermediate risk prostate cancer who are suitable for, and interested in, prostate brachytherapy, the opportunity to be randomized between low dose rate (LDR) brachytherapy using permanent implantation of radioactive seeds (the current standard of care in BC) and high dose rate (HDR) or temporary brachytherapy which is also available as a standard of care in BC but only when used as a boost in addition with external beam radiotherapy. In addition, men will be offered the opportunity for testing the aggressiveness of their cancer using Cell Cycle Progression Gene Profile.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Purpose:

To conduct a Phase III randomized trial for favorable tier intermediate risk prostate cancer and selected favorable risk tumors to evaluate the difference in Quality of Life in the urinary domain between LDR and HDR brachytherapy.

Hypothesis:

Because of more rapid dose delivery with HDR compared to LDR brachytherapy (15 minutes vs. 6 months) and more precise control of dose to adjacent critical structures (prostatic and bulbo-membranous urethra and anterior rectal wall), HDR prostate brachytherapy has been associated with more rapid recovery from acute symptoms and a more favorable side effect protocol when used as a boost in combination with external beam radiotherapy. The hypothesis is that this advantage will be maintained when brachytherapy is used as monotherapy without the addition of external beam radiation.

Justification:

In British Columbia, LDR prostate brachytherapy is the current standard for selected men with favorable risk prostate cancer who are not suitable for, or willing to accept active surveillance, and for men with favorable intermediate risk prostate cancer. LDR brachytherapy has been available in BC for over 15 years and is highly effective with 7-year biochemical disease-free rates of ~95%. However, this type of treatment has a prolonged recovery phase with return to baseline urinary function taking 6 to 12 months. This is partly due to the fact that the radiation is delivered over a 6 month period from the implanted seeds, and partly due to uncertainty in final seed placement. HDR brachytherapy has the advantage of delivering treatment very rapidly over 15-20 minutes, and also exploits the radiobiologic nature of prostate cancer which is more responsive to large doses of radiotherapy. Experience with using HDR brachytherapy as a boost has shown a much reduced impact on quality of life.

Objectives:

Primary: To evaluate the difference in QOL in the urinary domain between LDR and HDR brachytherapy using the urinary domain of the EPIC prostate cancer specific QOL questionnaire.

Secondary:

  • To assess differences in the bowel and sexual domains of the EPIC prostate cancer specific QOL questionnaire between the 2 treatments
  • To asses time to recovery of the IPS Score which is widely used to assess urinary function after prostate cancer treatment. The time to return to baseline +/- 3 points will be determined.
  • Acute and long-term toxicity will be graded using the Common Terminology Criteria for Adverse Events (CTCAE V4) at each follow up time point
  • TRUS- MRI fusion will be developed within our planning software to facilitate treatment planning
  • To assess treatment efficacy, PSA will be recorded every 6 months to 5 years and then annually to 10 years and prostate re-biopsy will be performed at 36 months after radiotherapy.

Optional:

For those patients consenting to targeted biopsies under anaesthesia at the start of their brachytherapy procedure (separate consent)

  • Verify MRI-TRUS fusion accuracy
  • Correlate Cell Cycle Progression scores with outcome.

Research Method:

Multiparametric MRI (mpMRI)will be performed on all men as a staging procedure to ensure appropriateness for brachytherapy as monotherapy (without the addition of external beam radiotherapy or hormone therapy). The value of mpMRI in staging prostate cancer is widely recognized. Previous studies have shown that over 90% of intermediate risk cancers are visible on mpMRI. The MR images will be fused with the planning trans rectal ultrasound (TRUS) for each patient, ensuring adequate dose coverage of the lesion.

For those patients consenting to optional biopsies under anesthesia, accuracy of the fusion will be verified by obtaining 2 biopsies of the visualized lesion under TRUS guidance at the start of the brachytherapy procedure.

Follow up is as per standard practice to assess urinary, bowel and sexual side effects. In addition to the standard forms, patients will also complete an EPIC questionnaire. The questionnaires are completed every 3 months for 1 year and then every 6 months to 3 years and then annually, as per the standard follow up schedule.

Once the biopsy material has been pathologically confirmed to contain the target lesion, the aggressiveness will be assessed through Cell Cycle Progression (CCP) Gene Profile testing.

Men may be randomized to the type of brachytherapy and decline the biopsies. This initial protocol is a Pilot that will test feasibility of the randomization (patient acceptance). The aim is to accrue 60 men over 18-24 months and if achieved then apply to expand to a total of 200 men.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y5L3
        • British Columbia Cancer Agency Center for the Southern Interior

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Clinical stage T1c-T2b, PSA < 20, Gleason < 8
  • ECOG 0-1

  • Low tier intermediate-risk prostate cancer is defined by;

    o a single NCCN intermediate risk factor (either Gleason 7(3+4) and PSA < 10 ng/ml OR Gleason 6 and PSA 10-20 ng/ml)

  • 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 tumour 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Low dose rate brachytherapy
Device: Radiation Low dose rate prostate brachytherapy is delivered under anaesthesia 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
Permanent implantation of radioactive Iodine-125 seeds under anesthesia with ultrasound guidance
Other Names:
  • LDR brachytherapy, seed brachytherapy
Experimental: High dose rate brachytherapy

Device: Radiation High dose rate prostate brachytherapy is delivered in 2 procedures, 2 weeks apart, also under anaesthesia, but no follow-up imaging visit is required.

HDR brachytherapy is also accomplished as an out-patient.
Radiation: High Dose Rate prostate brachytherapy
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
Other Names:
  • HDR brachytherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The difference in Quality of Life in the urinary domain between LDR and HDR brachytherapy.
Time Frame: 0-36 months
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
Time Frame: 0-36 months
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
Time Frame: 0-36 months
The IPS Score will be assessed at baseline, 1, 3, 6, 12, 24 and 36 months
0-36 months
Acute and long term toxicity
Time Frame: 0-10 years
Acute and long-term toxicity will be graded using the Common Terminology Criteria for Adverse Events (CTCAE V4) at each follow up time point
0-10 years
TRUS- MRI fusion
Time Frame: baseline
TRUS- MRI fusion will be developed within our planning software to facilitate treatment planning
baseline
Biochemical Outcome
Time Frame: 5-10 years
PSA will be recorded every 6 months to 5 years and then annually to 10 years
5-10 years
Histologic Outcome
Time Frame: 3 years
Prostate re-biopsy will be performed at 36 months to assess the local efficacy of treatment
3 years
Cell cycle progression score
Time Frame: one month
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.
one month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

British Columbia Cancer Agency

Investigators

  • Study Director: Ross Halperin, MD, British Columbia Cancer Agency Program Director

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2016

Primary Completion (Actual)

April 1, 2021

Study Completion (Anticipated)

April 1, 2026

Study Registration Dates

First Submitted

February 17, 2016

First Submitted That Met QC Criteria

February 24, 2016

First Posted (Estimate)

February 25, 2016

Study Record Updates

Last Update Posted (Actual)

May 22, 2023

Last Update Submitted That Met QC Criteria

May 19, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H15-02103

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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