Radiotherapy for High Risk Prostate Cancer

Recruiting at 11 trial locations

Overseen By Ashley Feng, M.Sc.

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Sir Mortimer B. Davis - Jewish General Hospital

Must be taking: Androgen suppression

Must not be taking: Anti-arrhythmics

Disqualifiers: Other malignancies, Small-cell carcinoma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 28 months

307 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that patients must not have received any cytotoxic anticancer therapy for prostate cancer before joining. If you are taking a 5-alpha-reductase inhibitor for benign prostatic hypertrophy, it must be stopped before randomization.

What data supports the effectiveness of the treatment for high-risk prostate cancer?

Research shows that combining high-dose-rate brachytherapy (a type of internal radiation) with external beam radiation therapy (a type of external radiation) can improve outcomes for prostate cancer patients, especially when the dose is increased. This combination has been shown to be more effective than using external beam radiation alone. ^{1 2 3 4 5}

Is radiotherapy for high-risk prostate cancer safe?

Research shows that combining high-dose-rate brachytherapy (a type of internal radiation) with external beam radiation therapy (a type of external radiation) is generally safe for treating prostate cancer, though some patients may experience side effects like urinary or bowel issues. ^{1 2 5 6 7}

How is the treatment EBRT + HDR brachytherapy boost different for high-risk prostate cancer?

This treatment combines external beam radiation therapy (EBRT) with a high-dose-rate (HDR) brachytherapy boost, which allows for a higher, more targeted dose of radiation directly to the prostate. This approach is unique because it aims to increase the effectiveness of radiation therapy by delivering a concentrated dose to the cancer while minimizing exposure to surrounding healthy tissue. ^{1 2 3 4 6}

Research Team

Dr. Tamim Niazi, MDCM

Principal Investigator

Jewish General Hospital, McGill University

Eligibility Criteria

Men with high risk prostate cancer diagnosed within the last 6 months, having a clinical stage of T3/T4, Gleason Score >8, or PSA >20. They must have no metastases on scans and can't have had previous chemotherapy for prostate cancer. Prior hormone therapy is allowed if started less than 28 days before joining. Men with severe heart failure, hip replacements, certain allergies or other serious health issues are excluded.

Inclusion Criteria

My prostate cancer is advanced with a high Gleason score or PSA level.

My recent scans showed no cancer in my pelvic or para-aortic lymph nodes.

My recent scans show no signs of cancer spread.

Exclusion Criteria

I have not had pelvic radiotherapy or have conditions like severe bladder issues.

I do not have any serious illness or condition that would prevent me from following the study's treatment plan.

You are allergic to any of the study medications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either hypofractionated dose escalation radiotherapy or standard fractionation radiotherapy with HDR brachytherapy boost, along with 28 months of androgen deprivation therapy

28 months

Regular visits as per treatment protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment, including digital rectal examination and evaluation of testosterone and PSA levels

13 years

Monthly for the first month, every 4 months for the first 2 years, every 6 months for the third year, then annually for 10 years

Treatment Details

Interventions

• Androgen deprivation therapy
• EBRT + HDR brachytherapy boost
• Hypofractionated Dose Escalation Radiotherapy

Trial Overview This trial compares two radiation treatments for high risk prostate cancer: standard pelvic external beam radiation plus HDR brachytherapy boost versus hypofractionated dose escalation radiotherapy. The study aims to determine which method is safer and more effective by randomly assigning participants to one of the two treatment plans.

Participant Groups

Group I: ADT+EBRT+ HDR brachytherapy boost Experimental Treatment 2 Interventions

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).

Group II: ADT+Hypofractionated Dose Escalation RT Active Control 2 Interventions

Hypofractionated dose escalation radiotherapy: 68 Gy in 25 fractions in conjunction with 28 months of androgen deprivation therapy (ADT).

Who Is Running the Clinical Trial?

Sir Mortimer B. Davis - Jewish General Hospital

Lead Sponsor

Trials

61

Recruited

25,800+

Findings from Research

In a study of 101 patients with localized prostate cancer, high-dose rate brachytherapy (HDR) combined with external beam radiation (EBRT) showed promising early efficacy, with 82% of patients free from cancer recurrence after a median follow-up of 56 months.

While there were some significant acute toxicities, such as clot retention and a few serious complications, the long-term side effects were relatively low, with only 8% experiencing late grade 2 genitourinary toxicity and no late grade 3 gastrointestinal toxicity observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HDR brachytherapy combined with external beam radiation for localised prostate cancer: early experience from the Sydney Cancer Centre. Whalley, D., Patanjali, N., Jackson, M., et al.[2018]

In a clinical trial involving 42 men with intermediate-risk prostate cancer, a treatment combining a single 15 Gy HDR brachytherapy boost with a five-fraction external beam radiation therapy (EBRT) resulted in a high biochemical disease-free survival rate of 95.5% after a median follow-up of 36 months.

The treatment demonstrated low toxicity, with only one case of acute Grade 3 gastrointestinal and genitourinary toxicity, and no significant differences in health-related quality of life across urinary, bowel, or sexual domains, suggesting it is a safe and effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IB clinical trial of 15 Gy HDR brachytherapy followed by hypofractionated/SBRT in the management of intermediate-risk prostate cancer. Den, RB., Greenspan, J., Doyle, LA., et al.[2023]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Hypofractionated conformal HDR brachytherapy in hormone naïve men with localized prostate cancer. Is escalation to very high biologically equivalent dose beneficial in all prognostic risk groups? [2006]

2. Australia pubmed.ncbi.nlm.nih.gov

HDR brachytherapy combined with external beam radiation for localised prostate cancer: early experience from the Sydney Cancer Centre. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

High-dose-rate brachytherapy boost for prostate cancer: Comparison of three different fractionation schemes. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Direct 2-arm comparison shows benefit of high-dose-rate brachytherapy boost vs external beam radiation therapy alone for prostate cancer. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Dose escalation improves cancer-related events at 10 years for intermediate- and high-risk prostate cancer patients treated with hypofractionated high-dose-rate boost and external beam radiotherapy. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

A phase IB clinical trial of 15 Gy HDR brachytherapy followed by hypofractionated/SBRT in the management of intermediate-risk prostate cancer. [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

Combined high dose rate brachytherapy and external beam radiotherapy for clinically localised prostate cancer. [2019]