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RecruitingInterventionalPhase 3

Androgen Suppression Combined With Elective Nodal Irradiation and Dose Escalated Prostate Treatment: A Non-Inferiority, Phase III Randomized Controlled Trial of Stereotactic Body Radiation Therapy Versus Brachytherapy Boost in Patients With Unfavourable Risk Localized Prostate Cancer

NCT ID: NCT06235697Sponsor: Canadian Cancer Trials GroupLast updated: 2026-04-14

Summary

This study is being done to answer the following question: Is the strategy to give higher doses of radiotherapy treatment over a shorter period of time using special equipment and fewer treatments (also known as Stereotactic Body Radiation Therapy or SBRT) as effective as usual external radiation therapy given with a brachytherapy boost (which involves radiation sources inserted directly into the prostate)?

Detailed description

The usual approach for patients with unfavourable prostate cancer who are not in a study is treatment with external beam radiation therapy (EBRT) to the pelvis and prostate in combination with hormone therapy (androgen deprivation therapy - ADT). To improve control of prostate cancer at risk of returning, additional treatment with a brachytherapy boost (insertion of radiation sources directly into the prostate) is recommended. For patients who get the usual approach for this cancer, about 89 out of 100 are free of cancer after 5 years.

Arms & interventions

  • RadiationRadiation

    46Gy / 23 fractions of EBRT to pelvis and prostate + LDR or HDR boost to prostate OR 25Gy / 5 fractions of EBRT to pelvis and prostate (ultrahypofractionation EBRT (SBRT)) + LDR or HDR boost to prostate. \+ Adjuvant ADT: Unfavourable Intermediate Risk: 6 months or High / Very High Risk: 24 months

  • RadiationRadiation SBRT only

    25Gy / 5 fractions to pelvis + 40 Gy / 5 fractions to prostate (SBRT) (ultrahypofractionation EBRT (SBRT))

  • DrugADT

    Assigned at enrollment

Outcome measures

Primary

  • To compare the progression-free survival (PFS) of SBRT versus conventional EBRT plus brachytherapy boost defined as time to biochemical failure, initiation of salvage therapy, local-regional recurrence, distant progression, or death

    Time frame: 8.6 years

Secondary

  • Safety and tolerability assessed by CTCAE v5.0

    Time frame: 8.6 years

  • PSA response at 4 years compared using a Cochran-Mantel-Haenszel (CMH) test

    Time frame: 8.6 years

  • Metastasis-free Survival compared using the Gray's test

    Time frame: 8.6 years

  • Cause-specific Survival compared using the Gray's test

    Time frame: 8.6 years

  • Overall Survival analysed using a Cox proportional hazards model and graphically described using the Kaplan-Meier method

    Time frame: 8.6 years

  • Participant-reported outcomes using EPIC-26 questionnaire

    Time frame: 8.6 years

  • Participant-reported tolerability using PRO-CTCAE questionnaire

    Time frame: 8.6 years

  • Economic Outcomes using EQ-5D-5L

    Time frame: 8.6 years

  • Economic Outcomes using FACIT-COST

    Time frame: 8.6 years

Eligibility criteria

Sex: MaleAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: * Histologically confirmed adenocarcinoma of the prostate diagnosed within the last 9 months * Participants with unfavourable risk prostate cancer are eligible according to the following NCCN classification guidelines (Version 4.2022 - May 10, 2022): • Unfavourable-intermediate risk - has one or more of the following: * 2 or 3 Intermediate Risk Factors (IRFs): cT2b-cT2c, Gleason 7 (grade group 2 or 3), and/or PSA 10-20 ng/ml; * Gleason 4+3 (grade group 3) * \> 50% biopsy cores positive • High risk - has one of the following: * cT3a * Gleason 8-10 (grade group 4 or 5) * PSA \> 20 ng/ml • Very-high risk - has at least one of the following: * cT3b-cT4 * Primary Gleason pattern 5 * 2 or 3 high risk features: cT3a, Gleason 8-10 (grade group 4 or 5), and/or PSA \> 20 ng/ml * \> 4 cores with Gleason 8-10 (grade group 4 or 5) * ECOG performance status of 0, 1 or 2 * Participants must be ≥ 18 years of age * Judged to be medically fit for brachytherapy * Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life and/or health utility questionnaires in either English, French or Spanish * Participants consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each participant must sign a consent form prior to enrollment in the trial to document their willingness to participate * Participants must be accessible for treatment and follow-up. Investigators must assure themselves the participants enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up * In accordance with CCTG policy, protocol treatment is to begin within 12 weeks of participant enrollment * Participants must be willing to take precautions to prevent pregnancy while on study * ADT (LHRH agonists, antagonists, or anti-androgens) for prostate cancer is permitted for up to 30 days before study enrollment * 5-alpha reductase inhibitors (5-ARI) are allowed, but baseline PSA will be corrected if 5-ARI use occurs within 6 months of enrollment * Participants may NOT have received other therapies including chemotherapy, PARPi, radioligand or other investigational drugs for prostate cancer * Participants 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 * Urinary function defined as International Prostate Symptom Score (IPSS) \< 20. Alpha blockers are allowed to treat baseline urinary function * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial Exclusion Criteria: * Prior pelvic radiotherapy * Contraindication to radical prostate radiotherapy (e.g. connective tissue disease or inflammatory bowel disease) * Anticoagulation medication (if unsafe to discontinue for gold seed insertion or brachytherapy implant) and/or prior or current bleeding diathesis * Prior steam vaporization (Rezum), transurethral resection of the prostate (TURP), prostatectomy (simple or radical), or any ablative therapy to the prostate (cryotherapy, HIFU, TULSA, focal laser ablation, photodynamic therapy) * Prostate volume \> 60cc before start of androgen deprivation therapy * Anatomy that would preclude precise brachytherapy implant (such as arch interference or large median lobe) * Evidence of castrate resistance (defined as a rising PSA \> 3.0 ng/ml while testosterone is \< 3.0 nmol/l) * Hip prosthesis (unilateral hip replacement is allowed if dose constrains can be reasonably achieved.

Study locations (46)

Kaiser Permanente-Deer Valley Medical Center

Antioch, California, 94531

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente Dublin

Dublin, California, 94568

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente-Fremont

Fremont, California, 94538

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente Fresno Orchard Plaza

Fresno, California, 93720

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente-Fresno

Fresno, California, 93720

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente-Modesto

Modesto, California, 95356

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente Oakland-Broadway

Oakland, California, 94611

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente-Oakland

Oakland, California, 94611

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente- Marshall Medical Offices

Redwood City, California, 94063

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente-Richmond

Richmond, California, 94801

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Rohnert Park Cancer Center

Rohnert Park, California, 94928

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente-Roseville

Roseville, California, 95661

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

The Permanente Medical Group-Roseville Radiation Oncology

Roseville, California, 95678

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente Downtown Commons

Sacramento, California, 95814

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente-South Sacramento

Sacramento, California, 95823

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente-San Francisco

San Francisco, California, 94115

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente-Santa Teresa-San Jose

San Jose, California, 95119

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente San Leandro

San Leandro, California, 94577

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser San Rafael-Gallinas

San Rafael, California, 94903

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, 95051

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente-Santa Rosa

Santa Rosa, California, 95403

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente Cancer Treatment Center

South San Francisco, California, 94080

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente-South San Francisco

South San Francisco, California, 94080

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente-Stockton

Stockton, California, 95210

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente Medical Center-Vacaville

Vacaville, California, 95688

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente-Vallejo

Vallejo, California, 94589

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Kaiser Permanente-Walnut Creek

Walnut Creek, California, 94596

Recruiting
Site Public Contact · Contact
Samantha A. Seaward · Principal Investigator

Memorial Hospital East

Shiloh, Illinois, 62269

Recruiting
Site Public Contact · Contact
Lannis E. Hall · Principal Investigator

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376

Recruiting
Site Public Contact · Contact
Lannis E. Hall · Principal Investigator

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141

Recruiting
Site Public Contact · Contact
Lannis E. Hall · Principal Investigator

Washington University School of Medicine

St Louis, Missouri, 63110

Recruiting
Site Public Contact · Contact
Lannis E. Hall · Principal Investigator

Siteman Cancer Center-South County

St Louis, Missouri, 63129

Recruiting
Site Public Contact · Contact
Lannis E. Hall · Principal Investigator

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, 63136

Recruiting
Site Public Contact · Contact
Lannis E. Hall · Principal Investigator

Billings Clinic Cancer Center

Billings, Montana, 59101

Recruiting
Site Public Contact · Contact
John M. Schallenkamp · Principal Investigator

Northwell Health/Center for Advanced Medicine

Lake Success, New York, 11042

Recruiting
Site Public Contact · Contact
Sang E. Sim · Principal Investigator

Manhattan Eye Ear and Throat Hospital

New York, New York, 10065

Recruiting
Site Public Contact · Contact
Sang E. Sim · Principal Investigator

Lenox Hill Hospital

New York, New York, 10075

Recruiting
Site Public Contact · Contact
Sang E. Sim · Principal Investigator

Saint Vincent Hospital

Erie, Pennsylvania, 16544

Recruiting
Site Public Contact · Contact
Zachary Horne · Principal Investigator

Jefferson Hospital

Jefferson Hills, Pennsylvania, 15025

Recruiting
Site Public Contact · Contact
Zachary Horne · Principal Investigator

Forbes Hospital

Monroeville, Pennsylvania, 15146

Recruiting
Site Public Contact · Contact
Zachary Horne · Principal Investigator

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212

Recruiting
Site Public Contact · Contact
Zachary Horne · Principal Investigator

West Penn Hospital

Pittsburgh, Pennsylvania, 15224

Recruiting
Site Public Contact · Contact
Zachary Horne · Principal Investigator

Wexford Health and Wellness Pavilion

Wexford, Pennsylvania, 15090

Recruiting
Site Public Contact · Contact
Zachary Horne · Principal Investigator

Bon Secours Saint Francis Medical Center

Midlothian, Virginia, 23114

Recruiting
Site Public Contact · Contact
Joseph D. Pennington · Principal Investigator

Bon Secours Cancer Institute at Reynolds Crossing

Richmond, Virginia, 23230

Recruiting
Site Public Contact · Contact
Joseph D. Pennington · Principal Investigator

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298

Recruiting
Site Public Contact · Contact
Alfredo I. Urdaneta · Principal Investigator