In North America, the number of new cases of prostate cancer increases every year. Many efforts have been made to develop more efficient and safer curative treatments for high risk prostate cancer patients. This phase III clinical trial is designed to compare the safety of a standard pelvic external beam radiation therapy (EBRT) combined with a high dose rate brachytherapy (HDRB) boost (direct insertion of radiation source over a period of minutes via flexible needles temporarily inserted in the prostate) to a shorter course of hypofractionated dose escalation radiotherapy (larger radiation dose per daily treatment) in patients with high risk prostate cancer. The investigators plan to recruit 296 patients across Quebec who will be randomized in either treatment plan.
In North America, the number of new cases of prostate cancer increases every year. To this day, the standard curative treatment for high risk prostate cancer patients is external beam radiation therapy (EBRT) combined with hormonal manipulation (Luteinizing hormone-releasing hormone LHRH agonists such as Eligard) to lower levels of testosterone to slow down or even stop the growth of prostate cancer. It has been recently demonstrated that combination of high dose rate brachytherapy (HDRB) boost (direct insertion of radiation source in the prostate for killing the tumor) to EBRT could be an effective treatment for prostate cancer patients. On the other hand, other recent studies have suggested that dose escalation and hypofractionated radiation delivery (larger radiation dose per daily treatment) can be more efficient than standard fractionation in prostate cancer patients. This phase III clinical trial is designed to compare the safety of a conventional pelvic EBRT combined with a HDRB boost (i.e. 46 Gy in 23 fractions followed by a 15-Gy HDRB boost) to a shorter course of hypofractionated dose escalation radiotherapy (i.e. 68 Gy in 25 fractions) in patients with high risk prostate cancer. The patients will be randomized to either of the two different courses of treatment. All the patients will be also treated with hormonal therapy for a total duration of 28 months (2 months before radiation therapy (RT), 2 months during RT and for 24 months after RT). The patients will undergo different test before the treatment, such as bone scan, blood test, CT scan and bone density. The patient's follow-up will be the first month after start of RT, every 4 months for the first 2 years, then every 6 months the third year and then annually for 10 years. On every visit, the patient will undergo digital rectal examination (DRE) as well as evaluation of testosterone and prostate specific antigen (PSA) levels. The safety of the new course of radiation therapy will be evaluated by the acute (at and before 90 days) and delayed toxicities (at 90 days, at 180 days and after) measured by Common Terminology Criteria for Adverse Events (CTCAE version 4). We will also determine Biochemical Failure Free Survival, Distant Metastasis Free Survival, Disease Specific Survival, Overall Survival and the Health-related Quality of Life using the Expanded Prostate Cancer Index Composite (EPIC). We will also monitor the development of gastrointestinal and genitourinary toxicities and establish the predictive value of PTEN deletion and TMPRSS2ETS fusion (genetic markers to predict the nature and progression of prostate tumors). This study will be conducted through the Genitourinary Radiation Oncology Group of Quebec (GROUQ) in 12 selected radiation oncology centers. We plan to recruit 296 patients across Quebec and the recruitment should be completed within 24 months of activation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
307
Standard radiotherapy (EBRT, 23 fractions) with the addition of High Dose-Rate (HDR) brachytherapy boost within 3 weeks of beginning or finishing the EBRT.
Radiation therapy (higher radiation dose per treatment) will be given once a day, five days a week, over approximately 5 weeks.
28 months of androgen deprivation therapy (injections every 4 months for a total of 28 months)
Eastern Health
St. John's, Newfoundland and Labrador, Canada
Lawson Health Research Institute
London, Ontario, Canada
Windsor Regional Hospital
Windsor, Ontario, Canada
Centre Hospitalier des Vallées de l'Outaouais, Hôpital de Gatineau
Gatineau, Quebec, Canada
CHUM Notre-Dame
Montreal, Quebec, Canada
Montréal General Hospital
Montreal, Quebec, Canada
Jewish General Hospital, McGill University
Montreal, Quebec, Canada
CHUQ, L'Hôtel-Dieu de Québec
Québec, Quebec, Canada
Centre de santé Rimouski-Neigette
Rimouski, Quebec, Canada
CHUS - Hôpital Fleurimont
Sherbrooke, Quebec, Canada
...and 2 more locations
Acute and delayed toxicity differences measured by Common Terminology Criteria for Adverse Events (CTCAE) version 4.
Time frame: The acute toxicity will be evaluated at or before 90 days and for the delayed toxicity, it will be determined at 90 -180 days and after (persisting or appearing after 180 days).
Freedom from biochemical failure measured by PSA level.
an increase by 2 ng/mL or more above the nadir PSA is considered as biochemical failure
Time frame: At 3 and 5 years.
Rate of local failures measured by number of recurrences in the prostate.
Time frame: At 3 and 5 years.
Rate of regional failures measured by number of recurrences in the lymph nodes.
Time frame: At 3 and 5 years.
Rate of distant failures measured by number of metastases.
Time frame: At 3 and 5 years.
Disease specific survival measured by number of deaths associated to the prostate cancer.
Time frame: At 5 years.
Disease overall survival measured by the number of deaths after 5 years.
Time frame: At 5 years.
Health-related quality of life measured by using Expanded Prostate Cancer Index Composite (EPIC) questionnaire
Time frame: At every routine visit (baseline, 3 to 4 weeks after RT, every 4 months for 2 years, every 6 months the 3 following years and then annually until 10 years).
Correlation of dose-volume histogram of the rectum and bladder by studying wall and whole organ volumes to the development of gastrointestinal (GI) and genitourinary (GU) toxicity.
Time frame: At 180 days post treatment
Predictive value of the PTEN deletion and TMPRSS2-ETS gene fusion in high risk prostate cancer patients.
looking for correlation between these known gene mutations and local and/or distal recurrences.
Time frame: At the time when biopsy is done, < 6 months before randomization of participant
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