Phase II High Dose Brachytherapy and Low Dose Rate Brachytherapy as Monotherapy in Localized Prostate Cancer

A Randomized Phase II Trial Evaluating High Dose Rate Brachytherapy and Low Dose Rate Brachytherapy as Monotherapy in Localized Prostate Cancer

The purpose of this study is to evaluate the dose of High Dose Rate (HDR) brachytherapy chosen for this study as well as a commonly used alternate form of brachytherapy called low dose rate (or seed) brachytherapy. Investigators would like to understand how these treatments control the prostate cancer and look at their short and long term treatment related side effects.

The dose of radiation for HDR brachytherapy for this study has been changed since the study started. Other studies using the dose of radiation for HDR brachytherapy that was originally chosen for this study (Arm 2) found that this dose of radiation may be linked to a greater chance of the cancer coming back in the prostate. Therefore since March 2020, for new participants entering the study, a new HDR brachytherapy arm with a higher amount of radiation given over two doses will be tested in this study

Study Overview

• Status: Recruiting
• Conditions: Prostate Carcinoma
• Intervention / Treatment: Radiation: Low dose rate brachytherapy; Radiation: High dose rate brachytherapy

Detailed Description

Radiation therapy is an accepted treatment to help manage low and intermediate risk prostate cancer. Radiation therapy can be given using machines that are outside the body (called "image guided external beam radiation therapy") or by brachytherapy, which is a form of radiation therapy where the radiation source is placed directly into the prostate gland near the tumour. The standard or usual treatments for low or intermediate risk prostate cancer are low dose-rate (LDR) brachytherapy which involves placing radioactive seeds in the prostate which deliver radiation over several months, image guided external beam radiation therapy (IGRT), or IGRT plus high dose-rate (HDR) brachytherapy boost.

High Dose-Rate (HDR) brachytherapy is another type of brachytherapy which delivers a high dose of radiation to the tumour over a period of minutes. The radiation is delivered under computer control through flexible needles, which are temporarily inserted into the prostate. This form of radiotherapy targets cancer cells within the prostate gland. HDR brachytherapy is another type of radiotherapy for prostate cancer that has the potential to help target your cancer more accurately while causing fewer side effects compared with standard radiation therapy. HDR brachytherapy is an option for treatment in some hospitals now but the best dose of radiation is still unknown. This study is testing a new dose of radiation for HDR brachytherapy.

• Study Type: Interventional
• Enrollment (Estimated): 232
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wendy Parulekar; Phone Number: 613-533-6430; Email: wparulekar@ctg.queensu.ca

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • Ottawa Hospital Research Institute
      • Contact: Alain Haddad; Phone Number: 25395 613 737-7700
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • University Health Network
      • Contact: Srinivas Raman; Phone Number: 416 946-4501
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Odette Cancer Centre
      • Contact: Gerard Morton; Phone Number: 416 480-6165
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • The Jewish General Hospital
      • Contact: M. Tamim Niazi; Phone Number: 514 340-8288
    • Montreal, Quebec, Canada, H2X 3E4
      • Recruiting
      • CHUM-Centre Hospitalier de l'Universite de Montreal
      • Contact: Maroie Barkati; Phone Number: 514 890-8254
    • Quebec City, Quebec, Canada, G1R 2J6
      • Recruiting
      • Hotel-Dieu de Quebec
      • Contact: Eric Vigneault; Phone Number: 418 691-5264

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate diagnosed within the last 9 months. Patients on active surveillance with evidence of disease progression are eligible to the protocol as long as they meet the eligibility criteria and have a recent prostate biopsy (within 9 months).

• Patients with localized prostate cancer are eligible according to the following guidelines:

  • TNM classification:

  • Clinical stage T1-T2 and Gleason 6 and PSA <20 ng/mL
  • Clinical stage T1-T2 and Gleason 7 (3+4) and PSA < 15 ng/mL and ≤ 50% of positive nontargeted cores in patients who undergo systematic biopsy
• Eastern Cooperative Oncology Group status 0-1.
• Bone scan and pelvic CT scan/MRI within the last 6 months at the discretion of the treating physician.
• Patient must be ≥ 18 years of age.
• Judged to be medically fit for brachytherapy.
• Prostate volume by Trans-rectal Ultrasound (TRUS) or Magnetic Resonance Imaging (MRI) ≤ 60 cc within the last 6 months.
• American Urological Association (AUA) score ≤ 20 (alpha blockers allowed) within the last 4 weeks.
• Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French.
• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrolment in the trial to document their willingness to participate.
• Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre.
• In accordance with CCTG policy, protocol treatment is to begin within 12 weeks of patient randomization.
• Patients must be willing to take precautions to prevent pregnancy while on study.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

Exclusion Criteria:

• Prior or current bleeding diathesis.
• Previous androgen deprivation therapy (ADT).
• Alpha-reductase inhibitors (ARIs) within 90 days of randomization.
• Radical surgery for carcinoma of the prostate, prior pelvic radiation, prior chemotherapy for prostate cancer, prior TURP, prior cryosurgery of the prostate.
• Evidence of metastatic disease (radiology investigations at the discretion of the treating physician).
• Any serious active or co-morbid medical conditions, laboratory abnormality, psychiatric illness, active or uncontrolled infections, or serious illnesses or medical conditions that would prevent the patient from participating or to be managed according to the protocol (according to investigator's decision).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1 LDR; Low Dose Rate (LDR) brachytherapy with I-125 to a total dose of 144 Gy	Radiation: Low dose rate brachytherapy; I-125 to a total dose of 144 Gy
Active Comparator: Arm 3 HDR; High Dose Rate brachytherapy: 27 Gy in 2 fractions	Radiation: High dose rate brachytherapy; 27 Gy in 2 fractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of HDR and LDR brachytherapy on prostate cancer control as defined by 48 month PSA values	The primary endpoint of the study is prostate cancer control rate at 48 months. It is defined as the PSA <0.4ng/ml at 48 months. One sample binomial test will be used to test the 48 months disease control rate for each arm	48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival		7 years
Number and severity of adverse events	Acute and long term toxicity and safety including lower urinary tract symptoms	7 years
Quality of Life of patient and partner utilizing EPIC, PROMIS and R-DAS fatigue short form		7 years
Economic Analysis	Resource utilization and economic indices of treatment administration	7 years

Other Outcome Measures

Outcome Measure	Time Frame
Establish a comprehensive tumour bank linked to a clinical database for further studies of predictive and prognostic biomarkers in prostate cancer	7 years
PSA Progression - PSA nadir +2 ng/ml will be used to define biochemical failure and can only be declared at 36 months or beyond due to the phenomenon of PSA bounce	7 years
PSA nadir - Date PSA nadir +2 ng/ml is reached	7 years
Local disease progression - Clinically suspicious change in DRE with biopsy confirmation of progression or Urethral obstruction or bleeding necessitating a trans-urethral resection (TURP) only if resected tissue demonstrates malignancy	7 years
Regional disease progression - Prostate cancer progression involving the lymph nodes below the bifurcation of the common iliac arteries.	7 years
Distant disease progression - Evidence of prostate cancer by radiology or cytology or histology at sites remote from the prostate	7 years

Collaborators and Investigators

• Sponsor: Canadian Cancer Trials Group
• Investigators: Study Chair: Gerard Morton, Sunnybrook Health Sciences, Toronto ON; Study Chair: Eric Vigneault, Hotel Dieu de Quebec, Montreal, QC

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2017
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: November 7, 2016
• First Submitted That Met QC Criteria: November 7, 2016
• First Posted (Estimated): November 9, 2016

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: PR19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No