- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02594072
Androgen Suppression With Stereotactic Body or External Beam Radiation Therapy (ASSERT) (ASSERT)
Androgen Suppression With Stereotactic Body or External Beam Radiation Therapy (ASSERT): A Phase II Randomized Trial for Intermediate and High Risk Prostate Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The current study is a randomized phase II study comparing high speed, single arc, LINAC-based prostate stereotactic ablative radiotherapy (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:
- To determine the proportion of eligible patients who are willing to be randomized
- 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:
- To compare the disease free survival as reflected in biochemical relapse free survival at five years between the two interventions
- To compare the health related quality of life as reflected in changes on the EPIC questionnaire between the two interventions
- 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 radiotherapy 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 radiotherapy.
Assessments during radiotherapy:
All patients will be seen by a radiation oncologist (or clinical associate) weekly during radiotherapy. QOL assessment (EPIC), IPSS/SHIM, and adverse events assessment (CTCAEv4, modified Radiation Therapy Oncology Group (RTOG)/SOMA) will be done during week 5 of radiotherapy 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.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
British Columbia
-
Surrey, British Columbia, Canada, V3V1Z2
- BC Cancer Agency Fraser Valley Center
-
Victoria, British Columbia, Canada, V8R6V5
- BC Cancer Agency Vancouver Island Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Pathological diagnosis of prostate cancer within 365 days prior to registration.
Disease must be Canadian Consensus (GUROC) high and intermediate risk with probability of pelvic nodal involvements <15% by the Updated Partin Tables.
- High risk is defined by any of: ≥T3a, PSA > 20, or Gleason ≥ 8
- Intermediate risk is defined by: T1/T2 and/or Gleason ≤ 7 and/or PSA ≤20 and not low risk
- Disease must be T1 or T2 clinically
- Prostate specific antigen (PSA) and testosterone level (TTT) must be done not more than 60 days before registration. If androgen deprivation therapy is started before registration, PSA and TTT should be done not more than 60 days prior to commencement of androgen deprivation therapy.
- For high risk patients, negative pelvis CT scan and bone scan for metastases not more than 60 days before registration. If androgen deprivation therapy is started before registration, pelvis CT scan and bone scan should be done not more than 60 days prior to commencement of androgen deprivation therapy. For intermediate risk patients, pelvis CT scan and bone scan are optional.
- Commencement of androgen deprivation therapy is allowed before registration. However, the lead time must allow for completion of the radiation treatment within 6 months and 18 months of the androgen deprivation therapy treatment duration for intermediate and high risk disease respectively.
- History/physical examination with digital rectal examination of the prostate within 60 days of registration or commencement of androgen deprivation therapy.
- Life expectancy of at least 5 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
- No contraindication for 6 months and 18 months of androgen deprivation therapy respectively for intermediate and high risk disease.
Exclusion Criteria:
- Clinical evidence of extra-prostatic disease extension
- Clinical evidence of prostate volume > 90 cc prior to randomization
- Prior history of inflammatory bowel disease
- Prior history of invasive malignancy (except non-melanomatous skin cancer) or lymphomatous/hematogenous malignancy unless continually disease free for a minimum of 5 years. All patients with in situ carcinoma are eligible for this study (for example, carcinoma in situ of the oral cavity is eligible) except patients with carcinoma of the bladder (including in situ bladder cancer or superficial bladder cancer).
- Previous pelvic radiation
- Presence of a hip prosthesis
- Evidence of pelvic nodal involvement or distant metastases
Study Plan
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 |
---|---|
Experimental: SABR with androgen suppression
Stereotactic ablative radiotherapy (SABR) with a prescribed dose of 36.25 Gy in 5 fractions over 5 weeks (one treatment day per week).
Zoladex ® for androgen suppression, taken for 6 months for patients with intermediate-risk prostate cancer, 18 months for patients with high-risk prostate cancer.
|
Linac-based prostate stereotactic radiotherapy, using Volumetric Modulated Arc Therapy planning and delivery, with fiducial marker and cone-beam CT based image guidance.
The preferred agent for the protocol is goserelin acetate (Zoladex ®) 3-month depot, but other LHRH agonists are permitted.
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.
Other Names:
|
Active Comparator: EBRT with androgen suppression
Conventional external beam radiation therapy (EBRT) with a prescribed dose of 73.68 Gy in 28 fractions (5 treatment days per week over 5.5 weeks).
Zoladex ® for androgen suppression, taken for 6 months for patients with intermediate-risk prostate cancer, 18 months for patients with high-risk prostate cancer.
|
The preferred agent for the protocol is goserelin acetate (Zoladex ®) 3-month depot, but other LHRH agonists are permitted.
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.
Other Names:
Conventional intensity modulated radiotherapy, with fiducial marker or cone-beam CT based image guidance.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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.
Time Frame: 5 years
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of subjects with biochemical relapse free survival at five years as measured by PSA levels.
Time Frame: 5 years
|
5 years
|
To compare the health related quality of life as reflected in changes on the EPIC questionnaire between the two interventions
Time Frame: 5 years
|
5 years
|
To measure the mean prostate pre-fraction to post-fraction displacement, in millimeters, from CT scans done pre- and post-fraction.
Time Frame: at week 5 of radiotherapy (completion of radiotherapy)
|
at week 5 of radiotherapy (completion of radiotherapy)
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Abraham Alexander, MD, British Columbia Cancer Agency
- Principal Investigator: Winkle Kwan, MD, British Columbia Cancer Agency
Study record dates
Study Major Dates
Study Start
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ASSERT
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.
Clinical Trials on Prostate Cancer
-
Roswell Park Cancer InstituteRecruitingObesity | Overweight | Cancer Survivor | Prostate Adenocarcinoma | Stage I Prostate Cancer | Stage II Prostate Cancer | Stage III Prostate Cancer | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate Cancer | Stage IVA Prostate Cancer | Stage IVB Prostate Cancer | Stage A Prostate Cancer | Stage... and other conditionsUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Regeneron Pharmaceuticals; Prostate Cancer FoundationWithdrawnStage III Prostate Cancer | Stage IV Prostate Cancer | Stage IVA Prostate Cancer | Stage IVB Prostate Cancer | Stage IIIA Prostate Cancer | Stage IIIB Prostate Cancer | Stage IIIC Prostate Cancer
-
Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI)CompletedRecurrent Prostate Cancer | Stage I Prostate Cancer | Stage III Prostate Cancer | Adenocarcinoma of the Prostate | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
Jonsson Comprehensive Cancer CenterProgenics Pharmaceuticals, Inc.TerminatedRandomized Trial of PSMA PET Scan Before Definitive Radiation Therapy for Prostate Cancer (PSMA-dRT)Stage II Prostate Cancer AJCC v8 | Stage IIIA Prostate Cancer AJCC v8 | Stage IIIB Prostate Cancer AJCC v8 | Stage IIC Prostate Cancer AJCC v8 | Stage III Prostate Cancer AJCC v8 | Stage IIIC Prostate Cancer AJCC v8 | Stage IIA Prostate Cancer AJCC v8 | Stage IIB Prostate Cancer AJCC v8 | Stage I Prostate...United States
-
Ryan Kohlbrenner, MDRadiological Society of North AmericaCompletedProstate Adenocarcinoma | Stage IV Prostate Cancer AJCC v8 | Prostate Carcinoma | Stage IIIA Prostate Cancer AJCC v8 | Stage IIIB Prostate Cancer AJCC v8 | Stage IIC Prostate Cancer AJCC v8 | Stage III Prostate Cancer AJCC v8 | Stage IIIC Prostate Cancer AJCC v8 | Stage IVA Prostate Cancer AJCC v8 | Stage...United States
-
University of Southern CaliforniaNational Cancer Institute (NCI); SanofiTerminatedDiarrhea | Recurrent Prostate Cancer | Hormone-resistant Prostate Cancer | Stage I Prostate Cancer | Stage III Prostate Cancer | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
Mayo ClinicNational Cancer Institute (NCI)WithdrawnStage I Prostate Cancer AJCC v8 | Stage II Prostate Cancer AJCC v8 | Stage IIIA Prostate Cancer AJCC v8 | Stage IIIB Prostate Cancer AJCC v8 | Stage IIC Prostate Cancer AJCC v8 | Stage III Prostate Cancer AJCC v8 | Stage IIIC Prostate Cancer AJCC v8 | Stage IIA Prostate Cancer AJCC v8 | Stage IIB Prostate...United States
-
Barbara Ann Karmanos Cancer InstituteGenentech, Inc.CompletedRecurrent Prostate Cancer | Stage I Prostate Cancer | Stage III Prostate Cancer | Adenocarcinoma of the Prostate | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
Ohio State University Comprehensive Cancer CenterRiverside Methodist HospitalCompletedStage I Prostate Cancer | Stage III Prostate Cancer | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
University of California, IrvineCompletedRecurrent Prostate Cancer | Stage I Prostate Cancer | Stage III Prostate Cancer | Adenocarcinoma of the Prostate | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
Clinical Trials on stereotactic ablative radiotherapy
-
Lawson Health Research InstituteOntario Institute for Cancer ResearchActive, not recruiting
-
Barts & The London NHS TrustRecruitingHeart Failure | Ventricular Tachycardia | Radiotherapy; Complications | Structural Heart AbnormalityUnited Kingdom
-
University Health Network, TorontoRecruiting
-
Second Xiangya Hospital of Central South UniversityCompletedSterEotactic AbLative Radiotherapy in PatiEnts With HypertrophiC ObstrucTive Cardiomyopathy (SELECT)Hypertrophic Obstructive CardiomyopathyChina
-
Lawson Health Research InstituteUniversity of British Columbia; Western University, Canada; London Health Sciences...Active, not recruitingNon Small Cell Lung Cancer | Interstitial Lung DiseaseCanada, United Kingdom
-
National Taiwan University HospitalUnknownMetastasis of Malignant Neoplasm to Lymph NodeTaiwan
-
European Institute of OncologyAssociazione Italiana per la Ricerca sul CancroRecruiting
-
Stanford UniversityVarian, a Siemens Healthineers CompanyActive, not recruitingEmphysemaUnited States
-
European Organisation for Research and Treatment...UnknownNon-small Cell Lung Cancer Stage I | Non-small Cell Lung Cancer Stage IIGermany, Belgium, United Kingdom, Switzerland