Official Title
Androgen Suppression With Stereotactic Body or External Beam Radiation Therapy (ASSERT): A Phase II Randomized Trial for Intermediate and High Risk Prostate Cancer
Summary:
Two radiation therapy techniques are commonly used for the treatment of intermediate and
high risk prostate cancer: brachytherapy and external beam radiation therapy (EBRT).
However, both have limitations. Brachytherapy, in which radioactive seeds are inserted into
the prostate, produces excellent outcomes but is invasive and not all patients are eligible
or willing to receive this treatment. EBRT, while gentle at the time of delivery, tends to
be very prolonged and may have poorer outcomes than brachytherapy. This study will examine
the use of stereotactic ablative radiation therapy (SABR), in which patients are given only a
few, high dose radiation treatments. Treatments are short, non-invasive, applicable to
patients not able to do brachytherapy, and may be more effective than conventional EBRT.
This study will compare SABR with EBRT in terms of the rates of acute and late toxicities
for each treatment, disease-free survival, and health-related quality of life measures.
Trial Description
Primary Outcome:
- Number of subjects experiencing treatment-related acute and late toxicities, focussing on grade 3 and 4 complications, as assessed by the NCI CTCAEv4 and modified RTOG/SOMA toxicity scale.
Secondary Outcome:
- Number of subjects with biochemical relapse free survival at five years as measured by PSA levels.
- To compare the health related quality of life as reflected in changes on the EPIC questionnaire between the two interventions
- To measure the mean prostate pre-fraction to post-fraction displacement, in millimeters, from CT scans done pre- and post-fraction.
The current study is a randomized phase II study comparing high speed, single arc,
LINAC-based prostate stereotactic ablative radiation therapy (SABR) with conventional external
beam radiation treatment (EBRT), along with androgen suppression (AS), in men with
intermediate and high risk prostate cancer, who are either unsuitable for or unwilling to
have brachytherapy. The two primary objectives of the study are to assess the feasibility of
randomization, and to compare the rates of acute and late toxicities. Should randomization
prove feasible, and toxicities comparable, a future phase 3 trial will be pursued.
Primary objectives:
1. To determine the proportion of eligible patients who are willing to be randomized
2. To estimate and compare the proportions of acute and late toxicities, focussing on
grade 3 and 4 complications of the treatment interventions as delivered in the British
Columbia (BC) Cancer Agency
Secondary objectives:
1. To compare the disease free survival as reflected in biochemical relapse free survival
at five years between the two interventions
2. To compare the health related quality of life as reflected in changes on the EPIC
questionnaire between the two interventions
3. To quantify the degree of intra-fraction motion with the proposed SABR technique
Research Method
To determine the willingness of eligible patients to be randomized, a screening log
documenting the number of eligible subjects approached for participation will be maintained.
Subjects who are approached but who decline participation will undergo a short interview by
the Clinical Research Associate as to the reason for non-participation. The Clinical
Research Associate will read from a script with statements to make sure that subjects who
refuse the trial know that they are free to provide or not provide the reasons for declining
the trial and that their answers will not affect the care they will receive. They will be
asked to list up to five reasons for non-participation in the trial. At the conclusion of
the trial, qualitative analyses will be done for the reason of non-participation.
The two radiation treatment protocols, conventional EBRT and SABR, will be compared in a
randomized, phase II study.
Patients with biopsy-proven intermediate or high risk prostate cancer will be accrued. T3 or
T4 disease, men with International Prostate Symptom Score >20 and prostate volume > 90 cc
are not eligible. Men with high risk disease must have a <15% risk of pelvic lymph node
involvement to be eligible.
Eligible subjects will be identified by the treating oncologist and enrolled through the
clinical trials unit of the participating regional cancer centre. Once the consent form is
signed, a Study Entry Form will be sent to the trial administrative centre located at the
Vancouver Island Centre of the BC Cancer Agency. A Patient Identification Number will be
assigned and the patient will be randomized to a treatment arm. This study proposes that
eighty (80) patients be randomized in a 1:1 ratio.
Subjects randomized to Arm 1 (conventional EBRT) will receive 73.68 Gy in 28 fractions (5
treatment days per week over 5.5 weeks).
Subjects randomized to Arm 2 (SABR) will receive a prescribed dose of 36.25 Gy in 5
fractions over 5 weeks (one treatment day per week).
Subjects randomized to the SABR arm will undergo an additional procedure prior to radiation
treatment to place gold seed fiducials (placement of gold seed fiducials is optional in the
EBRT arm and is at the discretion of the treating centre).
Androgen-Deprivation Therapy (ADT) will be administered to all patients on both treatment
arms. ADT will consist of luteinizing hormone-releasing hormone (LHRH) agonist monotherapy,
but total androgen blockade is also permitted at the discretion of the treating oncologist.
The total duration of ADT will be 6 months for men with intermediate risk disease, and 18
months for those with high risk disease. ADT is to be initiated prior to the start of RT.
PATIENT ASSESSMENTS AND FOLLOWUP
Pre-radiotherapy assessment:
All patients must have a biopsy indicating prostate adenocarcinoma within 365 days of trial
registration. A full history and physical examination, with digital rectal examination, must
be done within 60 days of registration. CT scan of the abdomen and pelvis and nuclear
medicine bone scan must be done within 60 days of registration. Baseline PSA and
testosterone must be done not more than 60 days before registration and repeated in the week
before radiation therapy to document response to androgen deprivation therapy. Physician
assessment must be done within 60 days of randomization. Baseline QOL assessment (EPIC),
prostate symptom score (IPSS), and sexual health inventory (SHIM) are to be done prior to
the start of radiation therapy.
Assessments during radiation therapy:
All patients will be seen by a radiation oncologist (or clinical associate) weekly during
radiation therapy. QOL assessment (EPIC), IPSS/SHIM, and adverse events assessment (CTCAEv4,
modified Radiation Therapy Oncology Group (RTOG)/SOMA) will be done during week 5 of
radiation therapy for both Arms 1 and 2.
Post-radiotherapy assessment and follow-up:
All patients will be assessed 2 weeks and 8 weeks post-radiotherapy, then every 6 months
until 2 years, and then yearly until year 5. At each of these time points patients will
undergo physician assessment, PSA/testosterone, QOL assessment (EPIC), IPSS/SHIM, and
adverse events assessment (CTCAEv4, modified RTOG/SOMA).
Data Analysis
Actuarial rates of acute (defined as occurring ≤ 6 months after initiation of treatment) and
late (defined as occurring > 6 months after initiation of treatment) as well as the
prevalence of late toxicities at 1, 2 and 5 years will be determined. Grade 3 and 4
toxicities will be compared between intervention groups using exact test statistics (SAS
FREQ procedure, SAS Gary, NC). Stratified analyses will also use the SAS FREQ procedure and
Zelen's exact test for equal odds ratios, exact confidence limits for the common odds ratio,
and an exact test for the common odds ratio. Quality of life scores and EPIC scales will be
compared between interventions using the t-test statistic.
View this trial on ClinicalTrials.gov
