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Hypofractionated, Dose Escalation Radiotherapy for High Risk Adenocarcinoma of the Prostate

Primary Purpose

Prostate Cancer

Status
Unknown status
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
hypofractionation
conventional
Sponsored by
Sir Mortimer B. Davis - Jewish General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring radiation therapy, hypofractionation, hormonal therapy, high risk adenocarcinoma of the prostate

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Histologically confirmed adenocarcinoma of the prostate diagnosed within 6 months prior to randomization
  2. 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).
  3. 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.
  4. 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.
  5. 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.
  6. The patient may have received prior androgen suppression therapy provided that androgen suppression therapy commenced no more than 28 days prior to randomization.
  7. The patient must not have received any cytotoxic anticancer therapy for prostate cancer prior to randomization.
  8. ECOG performance status must be 0 or 1

  9. Hematology and biochemistry: should be done within 28 days prior to randomization:

    1. Hemoglobin > 100 g/L
    2. Absolute Neutrophils > 1.5 x 109/L
    3. Platelets > 100 x 109/L
    4. AST and/or ALT < 1.5 x Upper Limit of Normal (ULN)
    5. Alkaline phosphatase < 2.5 x Upper Limit of Normal (ULN)
    6. Total bilirubin < ULN
    7. Serum creatinine < 1.5 x ULN
  10. adequate birth control measures should be used by the participant
  11. Patient consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements.
  12. Patients must be accessible for treatment and follow-up.

Exclusion Criteria:

  1. 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.
  2. The presence of small-cell or transitional-cell carcinoma in the biopsy specimen.
  3. Patients who had previous chemotherapy for carcinoma of the prostate.
  4. Patients who had prior surgical treatment for carcinoma of the prostate apart from trans-urethral resection, including bilateral orchiectomy.
  5. Patients with any contraindication to pelvic radiotherapy: including, but not limited to, previous pelvic radiotherapy, inflammatory bowel disease or severe bladder irritability.
  6. Patients with serious non malignant disease resulting in a life expectancy less than 3 years.
  7. Other serious illness, psychiatric or medical condition that would not permit the patient to be managed according to the protocol
  8. Known hypersensitivity to any protocol-indicated study medications.
  9. Presence of bilateral hip replacement prostheses.

Sites / Locations

  • Horizon Health Network - Saint John Regional Hospital
  • Complexe hospitalier de la Sagamie
  • Hôpital de Gatineau
  • Hôpital Charles-Lemoyne
  • Hôpital de la Cité-de-la-santé de Laval
  • CHUM-Notre- Dame
  • Hôpital Maisonneuve-Rosemont
  • Jewish General Hospital
  • Centre de santé Rimouski-Neigette
  • CHUS - Hôpital Fleurimont
  • Centre Hospitalier régional de Trois-Rivières
  • CHUQ, L'Hôtel-Dieu de Québec

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Hypofractionation

Conventional

Arm Description

One phase technique (IMRT or 3D-CRT): radiotherapy to the prostate + pelvic lymphnodes

two-phase technique (IMRT or 3D-CRT): 1) whole pelvis including the prostate and regional lymph nodes; 2) boost to the prostate

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

freedom from biochemical failure
To measure freedom from biochemical failure at 3 and 5 years.
disease free and overall survival
To measure disease specific and overall survival 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.

Full Information

First Posted
September 29, 2011
Last Updated
October 19, 2020
Sponsor
Sir Mortimer B. Davis - Jewish General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01444820
Brief Title
Hypofractionated, Dose Escalation Radiotherapy for High Risk Adenocarcinoma of the Prostate
Official Title
Phase III Study of Hypofractionated, Dose Escalation Radiotherapy for High Risk Adenocarcinoma of the Prostate, Using 3D-CRT or Intensity-Modulated Radiotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 2012 (Actual)
Primary Completion Date
January 2022 (Anticipated)
Study Completion Date
January 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sir Mortimer B. Davis - Jewish General Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
radiation therapy, hypofractionation, hormonal therapy, high risk adenocarcinoma of the prostate

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
329 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hypofractionation
Arm Type
Experimental
Arm Description
One phase technique (IMRT or 3D-CRT): radiotherapy to the prostate + pelvic lymphnodes
Arm Title
Conventional
Arm Type
Other
Arm Description
two-phase technique (IMRT or 3D-CRT): 1) whole pelvis including the prostate and regional lymph nodes; 2) boost to the prostate
Intervention Type
Radiation
Intervention Name(s)
hypofractionation
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
conventional
Intervention Description
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.
Primary Outcome Measure Information:
Title
Acute and delayed genito-urinary and gastrointestinal toxicity differences
Description
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.
Time Frame
6-8 years
Secondary Outcome Measure Information:
Title
freedom from biochemical failure
Description
To measure freedom from biochemical failure at 3 and 5 years.
Time Frame
3 years and 5 years post-treatment
Title
disease free and overall survival
Description
To measure disease specific and overall survival at 5 years
Time Frame
at 5 years
Title
Correlation of rectum and bladder Distribution Volume Histogram (DVH) to toxicities
Description
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.
Time Frame
at 180 days post treatment

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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. Exclusion Criteria: 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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tamim Niazi, MD
Organizational Affiliation
Jewish General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Horizon Health Network - Saint John Regional Hospital
City
Saint John
State/Province
New Brunswick
Country
Canada
Facility Name
Complexe hospitalier de la Sagamie
City
Chicoutimi
State/Province
Quebec
Country
Canada
Facility Name
Hôpital de Gatineau
City
Gatineau
State/Province
Quebec
Country
Canada
Facility Name
Hôpital Charles-Lemoyne
City
Greenfield Park
State/Province
Quebec
Country
Canada
Facility Name
Hôpital de la Cité-de-la-santé de Laval
City
Laval
State/Province
Quebec
Country
Canada
Facility Name
CHUM-Notre- Dame
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
Hôpital Maisonneuve-Rosemont
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
Centre de santé Rimouski-Neigette
City
Rimouski
State/Province
Quebec
Country
Canada
Facility Name
CHUS - Hôpital Fleurimont
City
Sherbrooke
State/Province
Quebec
Country
Canada
Facility Name
Centre Hospitalier régional de Trois-Rivières
City
Trois-Rivières
State/Province
Quebec
Country
Canada
Facility Name
CHUQ, L'Hôtel-Dieu de Québec
City
Quebec
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
33577365
Citation
Khriguian 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.
Results Reference
derived

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Hypofractionated, Dose Escalation Radiotherapy for High Risk Adenocarcinoma of the Prostate

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