Ignite Creation Date:
2024-05-05 @ 11:45 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00129025
Status:
COMPLETED
Last Update Posted:
2011-10-10
First Post:
2005-08-09
Brief Title:
Hypofractionated Radiotherapy 55 Gy16 Fractions4 Weeks for Localized Prostate Cancer
Sponsor:
Alberta Health services
Organization:
AHS Cancer Control Alberta
Study Overview
Official Title:
A Phase III Study of Escalated-Dose Short-Course Hypofractionated Radiotherapy 55 Gy16 Fractions4 Weeks for Localized Prostate Cancer
Status:
COMPLETED
Status Verified Date:
2011-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Many patients with localized prostate cancer choose radiotherapy for treatment Recent improvements in technology have lead to better outcomes with less side effects and better disease control rates by allowing high doses of radiation to be delivered to the cancer with lower doses to surrounding healthy tissues Currently patients are required to attend daily treatments over seven to eight weeks which can be costly and disruptive for patients especially those not living close to a cancer centre
There is recent research that suggests that the same or better outcomes might be achieved in prostate cancer by delivering a smaller number of treatments but with a higher dose of radiation given on each visit over a shorter time than the usual seven to eight weeks
In this study the investigators propose to treat patients with prostate cancer using 16 treatments over four weeks thus reducing the number of visits to the cancer centre for treatment by 50
There is recent research that suggests that the same or better outcomes might be achieved in prostate cancer by delivering a smaller number of treatments but with a higher dose of radiation given on each visit over a shorter time than the usual seven to eight weeks
In this study the investigators propose to treat patients with prostate cancer using 16 treatments over four weeks thus reducing the number of visits to the cancer centre for treatment by 50
Detailed Description:
Purpose
To determine the acute and late effects of high-dose short-course hypofractionated radiotherapy of 55 Gy16 fraction4 weeks in the treatment of localized prostate cancer
To provide clinical data for confirmation of current linear-quadratic radiobiological model of fractionation sensitivity in the treatment of prostate cancer by external beam radiotherapy
Radiotherapy for Prostate Cancer
In 2003 18800 Canadians were expected to be diagnosed with prostate cancer 2000 of whom were in Alberta Prostate cancer represents a significant workload in most Canadian cancer centres At the Cross Cancer Institute CCI approximately 400 patients underwent a radical course of external beam radiotherapy in 2002 Typically each course of radiation consisted of 35 fractions given over 7 weeks Assuming an ideal efficiency of patient turnover on a given linear accelerator 3000 machine hours would be required to treat 400 patients
At present clinical trials are on-going to confirm that an increase in radiation dose given over 39-44 fractions per patient will be more efficacious than the current standard of 35-39 fractions Such an increase in radiation dose will require an increase in treatment capacity by 10 without increasing the number of patients treated
As an alternative to increasing the number of fractions to deliver a greater total dose the radiation dose given in each fraction can be increased Accordingly the total dose is decreased to maintain acceptable toxicity Such treatment schedule is referred to as hypofractionation
Hypofractionation in prostate cancer was studied in the Phase III NCIC Clinical Trials Group PR-5 study The long term outcomes were reported at ASTRO in November of 2003 The results of the PR-5 study together with a similar Australian randomized trial reported in 2003 strongly support the biological model of a high fractionation sensitivity of prostate cancer which can be exploited using hypofractionated radiotherapy
Hypofractionation - Choice of Dose-Fractionation and Treatment Planning
Hypofractionated radiotherapy schedules are designed based on the premise of biological equivalent dose modeled by the linear quadratic method Possible schedules to achieve equivalent results can be given over 10 to 30 fractions In 2002 and 2003 investigators from Toronto Ontario and Cleveland Ohio reported promising preliminary results based on 20 and 28 fractions per treatment course This technique takes advantage of modern CT-based treatment planning systems and technologies to precisely target the prostate with maximal sparing of adjacent normal tissues
In 2003 investigators from TBCC conducted a dosimetry study to determine the equivalent hypofractionated dose given over 16 fractions The results presented by this principal investigator at the European Cancer Conference in September 2003 and at the Canadian Association of Radiation Oncologists scientific meeting in October 2003 showed that a dose of 55 Gy in 16 fractions given over four weeks is a biologically equivalent course of treatment compared to current standard treatment over seven to eight weeks at the CCI
The hypothesis being tested in this study is that hypofractionated radiotherapy of 55 Gy16 fractions4 weeks will be well tolerated with acute and late toxicity comparable to conventional radiotherapy The secondary objective is to determine the rate of biochemical control and the need for complex treatment planning IMRT as opposed to 3D conformal therapy
Patient Population
Patients with low and intermediate risk prostate cancer are eligible for this study Specifically patients with clinical T1 or T2 Gleason score 6 and PSA 20 and patients with clinical T1-T2 Gleason score 7 and PS 15 are eligible
Treatment
Neoadjuvant hormonal therapy up to six months is allowed Radiation dose prescribed is 55 Gy in 16 fractions over four weeks four fractions per week CTV is the prostate - 05-1 cm of seminal vesicles PTV is the CTV plus 10 mm margin in all directions except posterior 5 mm
To ensure precise targeting using daily on-line imaging and correction of positioning prior to treatment fiducial markers will be inserted into the prostate under transrectal ultrasound TRUS guidance Three inert gold markers 098 mm diameter x 5 mm length will be implanted into the prostate apex mid-gland and base The procedure will follow similar guidelines as for a TRUS prostate biopsy
Treatment planning guidelines are provided for 3D planning as well as IMRT All patients are planned by 3D conformal technique and if the dosimetry is unsatisfactory IMRT will be used Failure to meet all dose-constraint criteria for normal tissues will exclude the patient from the trial Details of treatment planning are provided in the full study protocol
Radiation Delivery
With the use of fiducial markers isocentre placements ie targeting correction will be made to maintain a target error of no greater than 3 mm in the right-left and superior-inferior directions and no greater than 2 mm in the anterior-posterior directions All deviations will be recorded
Treatment Outcomes
Other outcomes include acute and late GUbladder and acute GIrectum toxicity as well as patient-assessed quality of life Prostate Cancer Index The percentage of patients requiring IMRT treatment will be determined The changes in rectal mucosa will be assessed by endoscopy for a subset of patients who agree to undergo sigmoidoscopy at baseline 18 months and then 36 months after radiotherapy Tumor control will be determined as PSA relapse free survival using the ASTRO consensus definition for PSA failure
Statistics and Safety Monitoring
The sample six is one of convenience Given the limitations imposed by the time required for treatment planning and completing trials the investigators estimate that one patientmonth can be accrued and treated at each of the three centres They anticipate 72 patients will be enrolled in the trial over a two year period This will allow estimation of the late toxicity rate with reasonable precision
Approximate confidence interval CI width assuming minimal sample size 72 based on exact binomial interval
Gr 3 4 toxicity rate 005 01 015 02 95 CI width 012 016 018 020
Given the potential for increased toxicity due to the larger dosefraction the investigators will implement early stopping rules for unacceptable acute toxicity Although the late toxicity is the endpoint of interest acute toxicity will be used as a proxy due to the length of time needed to determine late toxicities Acute GI and GU toxicity have been reported to be significant predictors of late toxicity by several investigators
The stopping rules were determined following the method of Thall Simon and Estey JCO 1996 20 The investigators assume that the apriori distribution for the toxicity rate can be described by Betal 13 20 ie mean toxicity rate 005 95 probability interval for toxicity rate is between 000 an d010 The trial would be stopped if the posterior distribution was such that
Pr toxicity rate 010data 080 - that is if it is very likely that the toxicity rate 10
Data Coordination
This study will be conducted in three cancer centres namely the Tom Baker Cancer Centre Calgary the Cross Cancer Institute Edmonton and the Saskatoon Cancer Centre Saskatoon All patient related data will be collected in the individual institution and forwarded to the TBCC the coordinating centre Grade 3 or 4 toxicity and serious adverse events will be monitored and discussed among the co-investigators Data entry and analysis will be performed at TBCC with statistical support from the Division of Population Health and Information at the centre
To determine the acute and late effects of high-dose short-course hypofractionated radiotherapy of 55 Gy16 fraction4 weeks in the treatment of localized prostate cancer
To provide clinical data for confirmation of current linear-quadratic radiobiological model of fractionation sensitivity in the treatment of prostate cancer by external beam radiotherapy
Radiotherapy for Prostate Cancer
In 2003 18800 Canadians were expected to be diagnosed with prostate cancer 2000 of whom were in Alberta Prostate cancer represents a significant workload in most Canadian cancer centres At the Cross Cancer Institute CCI approximately 400 patients underwent a radical course of external beam radiotherapy in 2002 Typically each course of radiation consisted of 35 fractions given over 7 weeks Assuming an ideal efficiency of patient turnover on a given linear accelerator 3000 machine hours would be required to treat 400 patients
At present clinical trials are on-going to confirm that an increase in radiation dose given over 39-44 fractions per patient will be more efficacious than the current standard of 35-39 fractions Such an increase in radiation dose will require an increase in treatment capacity by 10 without increasing the number of patients treated
As an alternative to increasing the number of fractions to deliver a greater total dose the radiation dose given in each fraction can be increased Accordingly the total dose is decreased to maintain acceptable toxicity Such treatment schedule is referred to as hypofractionation
Hypofractionation in prostate cancer was studied in the Phase III NCIC Clinical Trials Group PR-5 study The long term outcomes were reported at ASTRO in November of 2003 The results of the PR-5 study together with a similar Australian randomized trial reported in 2003 strongly support the biological model of a high fractionation sensitivity of prostate cancer which can be exploited using hypofractionated radiotherapy
Hypofractionation - Choice of Dose-Fractionation and Treatment Planning
Hypofractionated radiotherapy schedules are designed based on the premise of biological equivalent dose modeled by the linear quadratic method Possible schedules to achieve equivalent results can be given over 10 to 30 fractions In 2002 and 2003 investigators from Toronto Ontario and Cleveland Ohio reported promising preliminary results based on 20 and 28 fractions per treatment course This technique takes advantage of modern CT-based treatment planning systems and technologies to precisely target the prostate with maximal sparing of adjacent normal tissues
In 2003 investigators from TBCC conducted a dosimetry study to determine the equivalent hypofractionated dose given over 16 fractions The results presented by this principal investigator at the European Cancer Conference in September 2003 and at the Canadian Association of Radiation Oncologists scientific meeting in October 2003 showed that a dose of 55 Gy in 16 fractions given over four weeks is a biologically equivalent course of treatment compared to current standard treatment over seven to eight weeks at the CCI
The hypothesis being tested in this study is that hypofractionated radiotherapy of 55 Gy16 fractions4 weeks will be well tolerated with acute and late toxicity comparable to conventional radiotherapy The secondary objective is to determine the rate of biochemical control and the need for complex treatment planning IMRT as opposed to 3D conformal therapy
Patient Population
Patients with low and intermediate risk prostate cancer are eligible for this study Specifically patients with clinical T1 or T2 Gleason score 6 and PSA 20 and patients with clinical T1-T2 Gleason score 7 and PS 15 are eligible
Treatment
Neoadjuvant hormonal therapy up to six months is allowed Radiation dose prescribed is 55 Gy in 16 fractions over four weeks four fractions per week CTV is the prostate - 05-1 cm of seminal vesicles PTV is the CTV plus 10 mm margin in all directions except posterior 5 mm
To ensure precise targeting using daily on-line imaging and correction of positioning prior to treatment fiducial markers will be inserted into the prostate under transrectal ultrasound TRUS guidance Three inert gold markers 098 mm diameter x 5 mm length will be implanted into the prostate apex mid-gland and base The procedure will follow similar guidelines as for a TRUS prostate biopsy
Treatment planning guidelines are provided for 3D planning as well as IMRT All patients are planned by 3D conformal technique and if the dosimetry is unsatisfactory IMRT will be used Failure to meet all dose-constraint criteria for normal tissues will exclude the patient from the trial Details of treatment planning are provided in the full study protocol
Radiation Delivery
With the use of fiducial markers isocentre placements ie targeting correction will be made to maintain a target error of no greater than 3 mm in the right-left and superior-inferior directions and no greater than 2 mm in the anterior-posterior directions All deviations will be recorded
Treatment Outcomes
Other outcomes include acute and late GUbladder and acute GIrectum toxicity as well as patient-assessed quality of life Prostate Cancer Index The percentage of patients requiring IMRT treatment will be determined The changes in rectal mucosa will be assessed by endoscopy for a subset of patients who agree to undergo sigmoidoscopy at baseline 18 months and then 36 months after radiotherapy Tumor control will be determined as PSA relapse free survival using the ASTRO consensus definition for PSA failure
Statistics and Safety Monitoring
The sample six is one of convenience Given the limitations imposed by the time required for treatment planning and completing trials the investigators estimate that one patientmonth can be accrued and treated at each of the three centres They anticipate 72 patients will be enrolled in the trial over a two year period This will allow estimation of the late toxicity rate with reasonable precision
Approximate confidence interval CI width assuming minimal sample size 72 based on exact binomial interval
Gr 3 4 toxicity rate 005 01 015 02 95 CI width 012 016 018 020
Given the potential for increased toxicity due to the larger dosefraction the investigators will implement early stopping rules for unacceptable acute toxicity Although the late toxicity is the endpoint of interest acute toxicity will be used as a proxy due to the length of time needed to determine late toxicities Acute GI and GU toxicity have been reported to be significant predictors of late toxicity by several investigators
The stopping rules were determined following the method of Thall Simon and Estey JCO 1996 20 The investigators assume that the apriori distribution for the toxicity rate can be described by Betal 13 20 ie mean toxicity rate 005 95 probability interval for toxicity rate is between 000 an d010 The trial would be stopped if the posterior distribution was such that
Pr toxicity rate 010data 080 - that is if it is very likely that the toxicity rate 10
Data Coordination
This study will be conducted in three cancer centres namely the Tom Baker Cancer Centre Calgary the Cross Cancer Institute Edmonton and the Saskatoon Cancer Centre Saskatoon All patient related data will be collected in the individual institution and forwarded to the TBCC the coordinating centre Grade 3 or 4 toxicity and serious adverse events will be monitored and discussed among the co-investigators Data entry and analysis will be performed at TBCC with statistical support from the Division of Population Health and Information at the centre
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None