Comparative Study of Radiotherapy Treatments to Treat High Risk Prostate Cancer Patients

September 20, 2021 updated by: Dr. Tamim Niazi, Sir Mortimer B. Davis - Jewish General Hospital

Phase III Study of Hypofractionated, Dose Escalation Radiotherapy vs. Conventional Pelvic Radiation Therapy Followed by HDR Brachy Boost for High Risk Adenocarcinoma of the Prostate (PCS-VI)

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.

Study Overview

Detailed Description

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

Enrollment (Anticipated)

296

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Newfoundland and Labrador
      • St-Johns, Newfoundland and Labrador, Canada, A1B 3V6
        • Recruiting
        • Eastern Health
        • Contact:
          • Dawne Putt
        • Principal Investigator:
          • Dr. Asim Kamran
        • Sub-Investigator:
          • Dr. John Thoms
    • Ontario
      • London, Ontario, Canada, N6C 2R5
        • Recruiting
        • Lawson Health Research Institute
        • Contact:
          • Julie Mayo
        • Principal Investigator:
          • David D'Souza, MD
      • Windsor, Ontario, Canada, N8W2X3
        • Recruiting
        • Windsor Regional Hospital
        • Contact:
          • Donna Clinansmith
        • Principal Investigator:
          • Junaid Yousuf
    • Quebec
      • Gatineau, Quebec, Canada, J8P 7H2
        • Recruiting
        • Centre Hospitalier des Vallées de l'Outaouais, Hôpital de Gatineau
        • Contact:
          • Marie-Pierre Desrosiers
        • Principal Investigator:
          • Marc Gaudet, MD
      • Montréal, Quebec, Canada, H1T 2M4
        • Withdrawn
        • Hopital Maisonneuve-Rosemont
      • Montréal, Quebec, Canada, H2L 4M1
        • Recruiting
        • CHUM Notre-Dame
        • Contact:
          • Chantal Lafleur
        • Principal Investigator:
          • Guila Delouya, MD
      • Montréal, Quebec, Canada, H3G 1A4
        • Recruiting
        • Montreal General Hospital
        • Principal Investigator:
          • Marie Duclos, MD
      • Montréal, Quebec, Canada, H3T 1E2
      • Québec, Quebec, Canada, G1R 2J6
        • Recruiting
        • CHUQ, L'Hôtel-Dieu de Québec
      • Rimouski, Quebec, Canada, G5L 5T1
        • Recruiting
        • Centre de santé Rimouski-Neigette
        • Contact:
          • Geneviève Néron
        • Principal Investigator:
          • Redouane Bettahar, MD
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Recruiting
        • CHUS - Hôpital Fleurimont
      • Trois-Rivières, Quebec, Canada, G8Z 3R9
        • Recruiting
        • Centre hospitalier regional de Trois-Rivieres
        • Principal Investigator:
          • Julie Harvey, MD
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4T 7T1
        • Recruiting
        • Allan Blair Cancer Centre
        • Contact:
          • Wendie Templeton
        • Principal Investigator:
          • Dr. Asim Amjad

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate diagnosed within 6 months prior to randomization, (if longer than 6 months, needs to be approved by the PI).
  • Clinical stage including at least one of the following: T3 or T4, Gleason Score > 8, and/ or Prostate-specific antigen (PSA) > 20 (ng/ml or μg/L).
  • Pelvic and para-aortic lymph nodes must be negative on CT scan or MRI of the abdomen and pelvis performed within 12 (recommended time limit, may exceed in certain cases) weeks prior to randomization. For patients who have started androgen suppression prior to randomization, CT or MRI may be done after start of therapy, provided it is done no more than 28 days following start of androgen suppression therapy (any lymph node appearing > 1.5 cm on CT or MRI must be histologically negative by either needle aspirate or lymph node dissection performed within 12 weeks prior to randomization).
  • Investigations, including chest x-ray (CXR is recommended and not mandatory) CT scan and bone scan (with radiographs of suspicious areas) have been performed within 12 weeks (recommended time limit) prior to randomization and are negative for metastases. For patients who have started androgen suppression prior to randomization, bone scan may be done up to and including 28 days after the commencement of therapy.
  • 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 PSA value used to confirm high risk disease and the value to be entered on the eligibility checklist must be the higher of these two values. These criteria will be the same regardless of whether or not the patient has initiated hormone therapy 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. Patients may have received treatment with a 5-alpha-reductase inhibitor (e.g. Finasteride) for benign prostatic hypertrophy (BPH), which must have been discontinued prior to the randomization.
  • ECOG performance status must be 0 or 1.
  • Hematology and Biochemistry: Laboratory requirements have been done within 28-42 days prior to randomization: hemoglobin > 100 g/L, absolute Neutrophils > 1.5 x 109/L, platelets > 100 x 109/L, serum creatinine < 1.5 x ULN

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 (at the discretion of the treating oncologist) 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 including active uncontrolled infection and significant cardiac dysfunction. Patients with medical conditions that would contraindicate the treatment regimen outlined in the protocol [e.g. intake of study drugs].
  • Known hypersensitivity to any protocol-indicated study medications.
  • Presence of bilateral hip replacement prostheses.
  • Patients with history of severe congestive heart failure will not be eligible.
  • Patients with congenital long QT syndrome or patients taking Class IA, Class III or Class IC anti-arrhythmic medications will require a cardiologist's evaluation prior to eligibility assessment. Patients with cardiovascular diseases can be included as long as the benefits of androgen deprivation therapy outweigh the potential risk of cardiovascular events.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: ADT+EBRT+ HDR brachytherapy boost
Standard fractionation radiotherapy: 46 Gy in 23 fractions (EBRT) and a 15-Gy HDRB boost in conjunction with 28 months of androgen deprivation therapy (ADT).
Standard radiotherapy (EBRT, 23 fractions) with the addition of High Dose-Rate (HDR) brachytherapy boost within 3 weeks of beginning or finishing the EBRT.
28 months of androgen deprivation therapy (injections every 4 months for a total of 28 months)
Other Names:
  • ADT
Active Comparator: ADT+Hypofractionated Dose Escalation RT
Hypofractionated dose escalation radiotherapy: 68 Gy in 25 fractions in conjunction with 28 months of androgen deprivation therapy (ADT).
28 months of androgen deprivation therapy (injections every 4 months for a total of 28 months)
Other Names:
  • ADT
Radiation therapy (higher radiation dose per treatment) will be given once a day, five days a week, over approximately 5 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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).
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).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Freedom from biochemical failure measured by PSA level.
Time Frame: At 3 and 5 years.
an increase by 2 ng/mL or more above the nadir PSA is considered as biochemical failure
At 3 and 5 years.
Rate of local failures measured by number of recurrences in the prostate.
Time Frame: At 3 and 5 years.
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.
At 3 and 5 years.
Rate of distant failures measured by number of metastases.
Time Frame: At 3 and 5 years.
At 3 and 5 years.
Disease specific survival measured by number of deaths associated to the prostate cancer.
Time Frame: At 5 years.
At 5 years.
Disease overall survival measured by the number of deaths after 5 years.
Time Frame: At 5 years.
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).
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
At 180 days post treatment
Predictive value of the PTEN deletion and TMPRSS2-ETS gene fusion in high risk prostate cancer patients.
Time Frame: At the time when biopsy is done, < 6 months before randomization of participant
looking for correlation between these known gene mutations and local and/or distal recurrences.
At the time when biopsy is done, < 6 months before randomization of participant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Tamim Niazi, MD, Jewish General Hospital, McGill University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2015

Primary Completion (Anticipated)

October 1, 2021

Study Completion (Anticipated)

January 1, 2029

Study Registration Dates

First Submitted

November 10, 2014

First Submitted That Met QC Criteria

November 24, 2014

First Posted (Estimate)

November 27, 2014

Study Record Updates

Last Update Posted (Actual)

September 21, 2021

Last Update Submitted That Met QC Criteria

September 20, 2021

Last Verified

September 1, 2021

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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