Trial Information

A Randomized Phase II Study Comparing Intensity Modulated External Beam Radiation Therapy (IMRT) Versus Permanent Interstitial Prostate Brachytherapy (PIPB) for Low Risk and Low-tier Intermediate Risk Prostate Cancer

Justification:

Patients with low risk and low-tier intermediate risk prostate cancer have a number of
different standard treatment options to chose from that include a radical prostatectomy,
conventional external beam radiotherapy (EBRT), or permanent interstitial prostate
brachytherapy (PIPB). Each of these treatment options have good outcomes, although they are
known to have a small risk of complications associated with each of them. Unfortunately,
these treatment options have never been directly compared and therefore it is difficult to
determine how these treatment options compare with respect to overall outcomes and toxicity.

A recent analysis from the BC Cancer Agency suggested that patients treated with
conventional EBRT within the Agency had inferior outcomes compared to PIPB. This data, as
well as other indirect evidence, suggest that conventional EBRT may be a suboptimal
treatment option compared to PIPB. Intensity modulated external beam radiotherapy (IMRT) is
a new technology that allows for the delivery of high doses of radiation that tightly
conforms to the target and limits the dose to surrounding critical structures. Although
IMRT is currently a standard therapeutic option that is utilized in other cancer sites at
the BC Cancer Agency, it has not been utilized in prostate cancer yet. Recent evidence has
confirmed that this experimental therapy is able to allow for the safe escalation of dose
for prostate cancer patients, which may lead to improved outcomes, without increasing
toxicity. There is no current evidence that side effects and complication risks associated
with IMRT are associated with any serious risk of increased toxicity, although this
continues to be studied.

This study will compare this new therapeutic approach (IMRT) directly with a standard
treatment option for prostate cancer patients (PIPB). This trial will allow us to determine
how the toxicities of these treatments compare with each other and, if successful, will
potentially lead to a larger study which will analyse how the outcomes of these therapeutic
interventions compare. We hope that this trial will make an important contribution to the
care and future management of patients with prostate cancer.

Objectives:

Primary Objective:

The primary end point of this study is the acute and late toxicities of the therapeutic
interventions.

Secondary Objectives:

This trial is also intended to determine:

- The willingness of eligible patients to be randomized to the treatment interventions.

- Obstacles to accrual that need to be addressed.

- Testing our ability to meet accrual targets.

- Checking quality assurance benchmarks for IMRT and PIPB procedures.

- Discovering and relieving bottlenecks in IMRT planning and procedures.

- Quality of life.

- Pathological local control.

- Biochemical relapse-free survival.

- Metastasis-free survival.

- Overall survival.

Research Method:

The patients will be randomly assigned with equal probability to one of two treatment arms:

Arm 1 (Control Arm) - Permanent interstitial prostate brachytherapy (PIPB). Arm 2
(Experimental Arm) - Intensity modulated external beam radiation therapy (IMRT).

Statistical Analysis:

Primary Endpoints:

Acute GI grade 3 or higher toxicity. Acute GU grade 3 or higher toxicity. Late GI grade 3 or
higher toxicity. Late GU grade 3 or higher toxicity.

Secondary Endpoints:

All acute and late toxicities. Quality of life scores (Using the expanded prostate cancer
index composite - EPIC).

Pathological local control. Biochemical relapse-free survival (using Phoenix definition).
Metastasis-free survival. Overall survival.

Planned sample size: 50 patients in total (i.e. 25 patients in each treatment arm).

Statistical analysis:

The two groups will be compared with respect to their primary and secondary endpoints.
Appropriate statistical analysis using a student t test for a statistical difference in
crude rates of grade 3 or higher toxicity between the two treatment arms will be performed.
All endpoints will be analysed for crude event rates with 95% confidence intervals for each
group.

With a sample size of only 50 patients, this trial is not powered to detect differences in
the incidence of common self-limited side effects and adverse reactions compared to standard
therapy. For this reason, the trial's limited power is augmented by a Trial Safety
Committee (TSC) which is bound by rules that require suspension/ termination of trial
accrual in the event of major complications (See Section 8.3 of Data Monitoring - Human
Ethics Application for Clinical Study or Part I: Section 5.3 on page 11 of the protocol).