Hypofractionated, Dose Escalation Radiotherapy for High Risk Adenocarcinoma of the Prostate
In North America, around a quarter a million men are diagnosed with prostate cancer every year, and about 31,000 patients will die of their disease each year. Like other western countries, the incidence in Canada has increased due to an aging population and prostate specific antigen (PSA) screening. This has led to a significant demand on cancer care services for these patients. Prostate cancer patient with high risk features are more often treated with external beam radiation therapy (EBRT) plus two to three years of hormonal manipulation (luteinizing hormone-releasing hormone [LHRH] agonist). The most common radiation dose treatment for these patients is 74-78 Gy in 37-39 daily fractions of 180-200 cGy for a treatment length of 7.5 weeks. This fraction size is believed to offer the best balance between desired tumour kill and unwanted normal tissue injury. Larger fraction sizes of more than 250 cGy (hypofractionation) are usually avoided for curative therapy because late reacting normal tissues. However prostate cancer cells have a unique radiobiology characteristic that suggests that hypofractionated radiotherapy is more efficient at prostate tumour killing than standard fractionation is, and will produce equivalent tumour control with a lower total dose and a shorter overall treatment time. Improved target localization techniques and conformal radiation therapy technology have allowed for dose escalation and hypofractionated radiation delivery in these circumstances with minimal or no increased toxicities.
This trial is designed to determine whether high risk prostate cancer patients can be safely treated with a dose escalation hypofractionated radiation therapy in 5 weeks as opposed to the usual 7-8 weeks. These patients will be randomized to either the usual 76 Gy in 38 fractions or 68 Gy in 25 fractions. 3D-Conformal Radiotherapy (3D-CRT) or Intensity Modulated Radiotherapy (IMRT) will be used to deliver the required radiation dose. Patients will also receive 28 months of androgen deprivation therapy (LHRH agonist). The primary outcome of the study is the acute and delayed toxicity and the secondary outcomes include biochemical failure, prostate specific mortality rate, bone metastases free survival, the prognostic and predictive value of several biological variables: presence of the PTEN deletion; expression of FoxP3 gene variants, topoisomerase 2α and cancer testis antigens; expression of X chromosome-linked micro-RNAs; presence of TMRSS2-ERG gene fusion and quality of life. It is planned to recruit 250 patients to this study.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase III Study of Hypofractionated, Dose Escalation Radiotherapy for High Risk Adenocarcinoma of the Prostate, Using 3D-CRT or Intensity-Modulated Radiotherapy|
- Acute and delayed genito-urinary and gastrointestinal toxicity differences [ Time Frame: 6-8 years ] [ Designated as safety issue: Yes ]primary outcome is the acute and delayed genito-urinary and gastrointestinal toxicity differences (at or before 90 days for the acute and 90-180 days and after for the delayed toxicity) in high risk prostate cancer patients treated with the hypofractionation vs standard of care regimen using 3D-CRT or IMRT.
- freedom from biochemical failure [ Time Frame: 3 years and 5 years post-treatment ] [ Designated as safety issue: No ]To measure freedom from biochemical failure at 3 and 5 years.
- disease free and overall survival [ Time Frame: at 5 years ] [ Designated as safety issue: No ]To measure disease specific and overall survival at 5 years
- Correlation of rectum and bladder Distribution Volume Histogram (DVH) to toxicities [ Time Frame: at 180 days post treatment ] [ Designated as safety issue: Yes ]To prospectively correlate dose-volume histograms of the rectum and bladder by studying wall and whole organ volumes to the development of GI and GU toxicity.
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||January 2023|
|Estimated Primary Completion Date:||January 2020 (Final data collection date for primary outcome measure)|
One phase technique (IMRT or 3D-CRT): radiotherapy to the prostate + pelvic lymphnodes
Centres using IMRT will use the dose painting technique to treat the prostate + proximal 1-cm SV to 6800 cGy in 25 fractions while the pelvic lymph nodes will receive 4500 cGy in 25 fractions. For patients with T3b, the whole SV is to be treated to 6800 cGy. Institutions using 3D-CRT will deliver the required dose to the pelvic volume (including pelvic lymph nodes and boost volume) - 4500 cGy - and a concomitant boost to the prostate and proximal 1-cm (or the whole SV if involved) SV to 6800 cGy.
two-phase technique (IMRT or 3D-CRT): 1) whole pelvis including the prostate and regional lymph nodes; 2) boost to the prostate
The first phase: whole pelvis including the prostate and regional lymph nodes treated with 4400 cGy in 22 fractions.
The second phase: prostate + proximal 1-cm SV treated with 3200 cGy in 16 fractions.
For patients with T3b, the whole SV is to be treated to 7600 cGy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01444820
|Canada, New Brunswick|
|Horizon Health Network - Saint John Regional Hospital|
|Saint John, New Brunswick, Canada|
|Complexe hospitalier de la Sagamie|
|Chicoutimi, Quebec, Canada|
|Hôpital de Gatineau|
|Gatineau, Quebec, Canada|
|Greenfield Park, Quebec, Canada|
|Hôpital de la Cité-de-la-santé de Laval|
|Laval, Quebec, Canada|
|Montreal, Quebec, Canada|
|Jewish General Hospital|
|Montreal, Quebec, Canada|
|Montreal, Quebec, Canada|
|Centre de santé Rimouski-Neigette|
|Rimouski, Quebec, Canada|
|CHUS - Hôpital Fleurimont|
|Sherbrooke, Quebec, Canada|
|Centre Hospitalier régional de Trois-Rivières|
|Trois-Rivières, Quebec, Canada|
|CHUQ, L'Hôtel-Dieu de Québec|
|Principal Investigator:||Tamim Niazi, MD||Jewish General Hospital|