Prostate CancerPhase 3NCT01444820
Hypofractionated, Dose Escalation Radiotherapy for High Risk Adenocarcinoma of the Prostate
A Phase 3 study testing hypofractionation and conventional in people with Prostate Cancer, run by Sir Mortimer B. Davis - Jewish General Hospital at 12 sites in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- hypofractionation and conventional
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 329 participants
- Where
- 12 sitesCanada
- Study dates
- Jan 2012to Jan 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed adenocarcinoma of the prostate diagnosed within 6 months prior to randomization
- Patient has been classified as high risk defined clinically as: T3 or T4, Gleason Score > 8, and/ or PSA > 20 (ng/mL or μg/L).
- Pelvic and para-aortic lymph nodes must be negative on computerized tomography (CT scan) or magnetic resonance imaging (MRI) of the abdomen and pelvis performed within 12 weeks prior to randomization.
- Investigations, including chest X-ray or chest CT scan and bone scan (with radiographs of suspicious areas) have been performed within 12 weeks prior to randomization and are negative for metastases.
- Patients will have had a PSA test done at the time of diagnosis. This PSA test could be repeated within 28 days prior to randomization.
- The patient may have received prior androgen suppression therapy provided that androgen suppression therapy commenced no more than 28 days prior to randomization.
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- The patient must not have received any cytotoxic anticancer therapy for prostate cancer prior to randomization.
- ECOG performance status must be 0 or 1
- Hematology and biochemistry: should be done within 28 days prior to randomization:
- Hemoglobin > 100 g/L
- Absolute Neutrophils > 1.5 x 109/L
- Platelets > 100 x 109/L
- AST and/or ALT < 1.5 x Upper Limit of Normal (ULN)
- Alkaline phosphatase < 2.5 x Upper Limit of Normal (ULN)
- Total bilirubin < ULN
- Serum creatinine < 1.5 x ULN
- adequate birth control measures should be used by the participant
- Patient consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements.
- Patients must be accessible for treatment and follow-up.
Who cannot join
- Patients with a history of other malignancies, except: non-melanoma skin cancer; or other solid tumours curatively treated with no evidence of disease for > 5 years.
- The presence of small-cell or transitional-cell carcinoma in the biopsy specimen.
- Patients who had previous chemotherapy for carcinoma of the prostate.
- Patients who had prior surgical treatment for carcinoma of the prostate apart from trans-urethral resection, including bilateral orchiectomy.
- Patients with any contraindication to pelvic radiotherapy: including, but not limited to, previous pelvic radiotherapy, inflammatory bowel disease or severe bladder irritability.
- Patients with serious non malignant disease resulting in a life expectancy less than 3 years.
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- Other serious illness, psychiatric or medical condition that would not permit the patient to be managed according to the protocol
- Known hypersensitivity to any protocol-indicated study medications.
- Presence of bilateral hip replacement prostheses.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Canada12 sites
Complexe hospitalier de la Sagamie
Chicoutimi, Quebec
Hôpital de Gatineau
Gatineau, Quebec
Hôpital Charles-Lemoyne
Greenfield Park, Quebec
Hôpital de la Cité-de-la-santé de Laval
Laval, Quebec
CHUM-Notre- Dame
Montreal, Quebec
Hôpital Maisonneuve-Rosemont
Montreal, Quebec
Jewish General Hospital
Montreal, Quebec
CHUQ, L'Hôtel-Dieu de Québec
Québec, Quebec
Centre de santé Rimouski-Neigette
Rimouski, Quebec
Horizon Health Network - Saint John Regional Hospital
Saint John, New Brunswick
CHUS - Hôpital Fleurimont
Sherbrooke, Quebec
Centre Hospitalier régional de Trois-Rivières
Trois-Rivières, Quebec
About this study
Official title: Phase III Study of Hypofractionated, Dose Escalation Radiotherapy for High Risk Adenocarcinoma of the Prostate, Using 3D-CRT or Intensity-Modulated Radiotherapy
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.
- Conditions
- Prostate Cancer
- Being tested
- hypofractionation, conventional
- Keywords
- radiation therapy, hypofractionation, hormonal therapy, high risk adenocarcinoma of the prostate
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hypofractionationRadiation
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.
conventionalRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| Hypofractionation | Experimental | One phase technique (IMRT or 3D-CRT): radiotherapy to the prostate + pelvic lymphnodes Receives: Radiation: hypofractionation |
| Conventional | Other | two-phase technique (IMRT or 3D-CRT): 1) whole pelvis including the prostate and regional lymph nodes; 2) boost to the prostate Receives: Radiation: conventional |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute and delayed genito-urinary and gastrointestinal toxicity differences
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.
Measured: 6-8 years
Secondary outcomes (3)
freedom from biochemical failure
To measure freedom from biochemical failure at 3 and 5 years.
Measured: 3 years and 5 years post-treatment
disease free and overall survival
To measure disease specific and overall survival at 5 years
Measured: at 5 years
Correlation of rectum and bladder Distribution Volume Histogram (DVH) to toxicities
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.
Measured: at 180 days post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2011 (estimated)
- Study startJan 2012
- Primary completionJan 2026 (estimated)
- Study completionJan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 329 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sir Mortimer B. Davis - Jewish General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Tamim Niazi, Sir Mortimer B. Davis - Jewish General Hospital
- Investigators
- Tamim Niazi, MD, Principal investigator, Jewish General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01444820
- Sponsor's protocol ID
- PCS V
- Status last verified
- Dec 2024
- First submitted
- 29 Sep 2011
- Last updated
- 4 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Niazi T, Nabid A, Malagon T, Bettahar R, Vincent L, Martin AG, Jolicoeur M, Yassa M, Barkati M, Igidbashian L, Bahoric B, Archambault R, Villeneuve H, Tsui JMG, Mohiuddin M. Hypofractionated, Dose Escalation Radiation Therapy for High-Risk Prostate Cancer: The Safety Analysis of the Prostate Cancer Study-5, a Groupe de Radio-Oncologie Genito-Urinaire de Quebec Led Phase 3 Trial. Int J Radiat Oncol Biol Phys. 2024 Jan 1;118(1):52-62. doi: 10.1016/j.ijrobp.2023.05.014. Epub 2023 May 22.
PubMed 37224928Khriguian J, Tsui JMG, Vaughan R, Kucharczyk MJ, Nabid A, Bettahar R, Vincent L, Martin AG, Jolicoeur M, Yassa M, Barkati M, Igidbashian L, Bahoric B, Archambault R, Villeneuve H, Mohiuddin M, Niazi T. The Clinical Significance of Bone Mineral Density Changes Following Long-Term Androgen Deprivation Therapy in Localized Prostate Cancer Patients. J Urol. 2021 Jun;205(6):1648-1654. doi: 10.1097/JU.0000000000001646. Epub 2021 Feb 12.
PubMed 33577365
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Study of Hypofractionated, Dose Escalation Radiotherapy for High Risk Adenocarcinoma of the Prostate, Using 3D-CRT or Intensity-Modulated Radiotherapy
- ClinicalTrials.gov ID
- NCT01444820
- Acronym / sponsor ID
- PCS V
- Conditions
- Prostate Cancer
- Keywords
- radiation therapy, hypofractionation, hormonal therapy, high risk adenocarcinoma of the prostate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 329 participants (actual)
- Lead sponsor
- Sir Mortimer B. Davis - Jewish General HospitalUniversity, hospital or other
- Study start
- Jan 2012 (actual)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Jan 2026 (estimated)
- First posted
- 3 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hypofractionation | Experimental | Radiation: hypofractionationOne phase technique (IMRT or 3D-CRT): radiotherapy to the prostate + pelvic lymphnodes |
| Conventional | Other | Radiation: conventionaltwo-phase technique (IMRT or 3D-CRT): 1) whole pelvis including the prostate and regional lymph nodes; 2) boost to the prostate |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Histologically confirmed adenocarcinoma of the prostate diagnosed within 6 months prior to randomization
- Patient has been classified as high risk defined clinically as: T3 or T4, Gleason Score > 8, and/ or PSA > 20 (ng/mL or μg/L).
- Pelvic and para-aortic lymph nodes must be negative on computerized tomography (CT scan) or magnetic resonance imaging (MRI) of the abdomen and pelvis performed within 12 weeks prior to randomization.
- Investigations, including chest X-ray or chest CT scan and bone scan (with radiographs of suspicious areas) have been performed within 12 weeks prior to randomization and are negative for metastases.
- Patients will have had a PSA test done at the time of diagnosis. This PSA test could be repeated within 28 days prior to randomization.
Key exclusion criteria (9 listed)
- Patients with a history of other malignancies, except: non-melanoma skin cancer; or other solid tumours curatively treated with no evidence of disease for > 5 years.
- The presence of small-cell or transitional-cell carcinoma in the biopsy specimen.
- Patients who had previous chemotherapy for carcinoma of the prostate.
- Patients who had prior surgical treatment for carcinoma of the prostate apart from trans-urethral resection, including bilateral orchiectomy.
- Patients with any contraindication to pelvic radiotherapy: including, but not limited to, previous pelvic radiotherapy, inflammatory bowel disease or severe bladder irritability.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hypofractionationCentres 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. | Radiation | Hypofractionation |
| conventionalThe 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. | Radiation | Conventional |
Primary outcome
Acute and delayed genito-urinary and gastrointestinal toxicity differences
Time frame: 6-8 years
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.
3 secondary outcomes
freedom from biochemical failure
Time frame: 3 years and 5 years post-treatment
disease free and overall survival
Time frame: at 5 years
Correlation of rectum and bladder Distribution Volume Histogram (DVH) to toxicities
Time frame: at 180 days post treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2024.
- Derived from this study: PubMed 37224928Niazi T, Nabid A, Malagon T, Bettahar R, Vincent L, Martin AG, Jolicoeur M, Yassa M, Barkati M, Igidbashian L, Bahoric B, Archambault R, Villeneuve H, Tsui JMG, Mohiuddin M. Hypofractionated, Dose Escalation Radiation Therapy for High-Risk Prostate Cancer: The Safety Analysis of the Prostate Cancer Study-5, a Groupe de Radio-Oncologie Genito-Urinaire de Quebec Led Phase 3 Trial. Int J Radiat Oncol Biol Phys. 2024 Jan 1;118(1):52-62. doi: 10.1016/j.ijrobp.2023.05.014. Epub 2023 May 22.
- Derived from this study: PubMed 33577365Khriguian J, Tsui JMG, Vaughan R, Kucharczyk MJ, Nabid A, Bettahar R, Vincent L, Martin AG, Jolicoeur M, Yassa M, Barkati M, Igidbashian L, Bahoric B, Archambault R, Villeneuve H, Mohiuddin M, Niazi T. The Clinical Significance of Bone Mineral Density Changes Following Long-Term Androgen Deprivation Therapy in Localized Prostate Cancer Patients. J Urol. 2021 Jun;205(6):1648-1654. doi: 10.1097/JU.0000000000001646. Epub 2021 Feb 12.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tamim Niazi, MD principal investigator
Jewish General Hospital
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing hypofractionation and conventional in people with Prostate Cancer, run by Sir Mortimer B. Davis - Jewish General Hospital at 12 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute and delayed genito-urinary and gastrointestinal toxicity differences (time frame: 6-8 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01444820, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2024.