Shorter Course Hormone + Radiation Therapy for High-risk Prostate Cancer

Recruiting at 6 trial locations

Overseen By Michael Zelefsky, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Bicalutamide, GnRH analogues

Disqualifiers: Metastatic disease, Prior pelvic radiation, others

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

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

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out whether combining a shorter than standard course of ADT with standard prostate brachytherapy and hypofractionated external beam radiation therapy is a safe and effective way to prevent high-risk prostate cancer from coming back and/or spreading to other parts of the body.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop taking your current medications. However, if you are already on ADT (androgen deprivation therapy) with bicalutamide and leuprolide or a similar medication, you can continue if it has been 60 days or less before joining the trial.

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

Research shows that combining androgen deprivation therapy (ADT) with radiation therapy can help reduce the risk of cancer returning and spreading in high-risk prostate cancer patients. ADT, when used with external beam radiation, has been associated with lower rates of cancer recurrence and distant metastasis. ^{1 2 3 4 5}

Is the combination of hormone therapy and radiation therapy safe for treating prostate cancer?

Hormone therapy combined with radiation therapy for prostate cancer is generally considered safe, but it can be associated with side effects such as those related to low testosterone levels. Studies have shown that while this combination improves survival outcomes, it can also lead to adverse events, so the duration and type of therapy should be carefully considered. ^{1 6 7 8 9}

How is the treatment of shorter course hormone and radiation therapy for high-risk prostate cancer different from other treatments?

This treatment is unique because it combines a shorter course of hormone therapy (which lowers male hormone levels) with a specific type of radiation therapy that includes both internal radiation (brachytherapy) and a more intense, shorter schedule of external beam radiation. This approach aims to reduce treatment time and potentially minimize side effects compared to longer hormone therapy durations. ^{1 2 3 6 10}

Research Team

Daniel Gorovets, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for men over 18 with high-risk prostate cancer, who haven't had certain other cancers in the last 2 years or treatments like TURP. They should be fit enough for anesthesia and have a life expectancy over 5 years. A genomic score ≤0.6 and no inflammatory bowel disease are also required.

Inclusion Criteria

My cancer's genetic score is 0.6 or lower.

My prostate is smaller than 90 cubic centimeters.

I started hormone therapy for cancer less than 60 days ago.

Exclusion Criteria

I do not have an active cancer that needs treatment, except for certain early-stage cancers.

My cancer has spread to lymph nodes or other parts of my body.

I have had surgery on my prostate.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Hormone Therapy

Participants receive androgen deprivation therapy (ADT) for 6 months, starting with bicalutamide 50 mg daily and leuprolide injections every 3 months

6 months

Brachytherapy

HDR prostate brachytherapy procedure performed approximately 3 months after starting ADT

1 day

Radiation Therapy

Participants receive image-guided, intensity-modulated, hypofractionated radiation therapy targeting the prostate, seminal vesicles, and pelvic lymph nodes

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Treatment Details

Interventions

• Androgen deprivation therapy (ADT)
• Brachytherapy
• Hypofractionated pelvic External beam radiation

Trial Overview The study tests if a shorter hormone therapy combined with standard brachytherapy (internal radiation) and hypofractionated external beam radiation can effectively prevent the return or spread of high-risk prostate cancer.

Participant Groups

Group I: Hormone Therapy and Radiation Experimental Treatment 3 Interventions

Patients enrolled in this study will receive ADT for 6 months which will consist of bicalutamide 50 mg PO daily starting approximately 1-2 weeks before leuprolide 22.5mg injected every 3 months. The HDR prostate brachytherapy procedure will be performed approximately 3 months after starting ADT to allow for potential radiosensitization and cytoreduction. Approximately 4 weeks after the HDR boost, patients will receive image-guided, intensity-modulated, hypofractionated radiation therapy targeting the prostate, seminal vesicles and pelvic lymph nodes to a dose of 25 Gy in 5 fractions delivered daily.

Androgen deprivation therapy (ADT) is already approved in European Union, United States, Canada, Japan, Switzerland for the following indications:

Approved in European Union as Androgen deprivation therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in United States as Androgen deprivation therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in Canada as Androgen deprivation therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in Japan as Androgen deprivation therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in Switzerland as Androgen deprivation therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Locally advanced prostate cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

In intermediate-risk prostate cancer patients (520 participants), androgen deprivation therapy (ADT) significantly improved biochemical relapse-free rates, particularly in those with multiple risk factors, indicating that short-term ADT (≤6 months) is beneficial.

For high-risk prostate cancer patients (555 participants), longer ADT durations (>6 months) were associated with better biochemical relapse-free rates, especially for those with multiple high-risk factors, suggesting that ADT for ≥21 months may be optimal when combined with high-dose proton beam therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal Androgen Deprivation Therapy Combined with Proton Beam Therapy for Prostate Cancer: Results from a Multi-Institutional Study of the Japanese Radiation Oncology Study Group. Murakami, M., Ishikawa, H., Shimizu, S., et al.[2020]

In a study of 1,290 high-risk prostate cancer patients treated with external beam radiation therapy, androgen deprivation therapy (ADT) significantly reduced the risk of biochemical failure and distant metastasis compared to no ADT, highlighting its efficacy in improving patient outcomes.

Patients receiving more than 24 months of ADT experienced a greater benefit in terms of PSA failure rates and distant metastasis-free survival, particularly in those who received low-dose radiation, suggesting that longer ADT duration may enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the Optimum Use of Androgen-Deprivation Therapy in High-Risk Prostate Cancer Patients Undergoing External Beam Radiation Therapy. Ludwig, MS., Kuban, DA., Strom, SS., et al.[2022]

In a study of 37 men with intermediate- or high-risk localized prostate cancer, a combination of 6 months of androgen-deprivation therapy (ADT) with abiraterone acetate and radiation therapy resulted in a 55% rate of undetectable prostate-specific antigen (PSA) levels at 12 months, indicating effective disease control.

The treatment was associated with manageable toxicity, primarily grade 3 hypertension in 32% of patients, and 81% of participants experienced testosterone recovery within a median time of 9.2 months, suggesting a favorable impact on quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Radiation Therapy and Short-Term Androgen Blockade With Abiraterone Acetate Plus Prednisone for Men With High- and Intermediate-Risk Localized Prostate Cancer. Koontz, BF., Hoffman, KE., Halabi, S., et al.[2021]

Patients with unfavorable intermediate- and high-risk prostate cancer who received extreme dose escalation with a combination of external beam radiotherapy (EBRT) and brachytherapy were significantly less likely to receive androgen deprivation therapy (ADT), with an odds ratio of 0.67, indicating a notable decrease in ADT utilization.

The study suggests a potential underutilization of ADT in higher-risk patients undergoing combined radiation treatments, highlighting the need for further prospective studies to clarify the role of ADT in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variations in patterns of concurrent androgen deprivation therapy use based on dose escalation with external beam radiotherapy vs. brachytherapy boost for prostate cancer. Mohiuddin, JJ., Narayan, V., Venigalla, S., et al.[2019]

Androgen deprivation therapy (ADT) significantly enhances biochemical control when combined with dose-escalated radiation therapy (RT) for prostate cancer, as supported by recent phase III studies.

There is now randomized evidence supporting the use of ADT alongside RT in patients who have undergone prostatectomy, highlighting its ongoing importance in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of Hormonal Therapy to Augment Radiation Therapy in Prostate Cancer: An Update. Kauffmann, G., Liauw, SL.[2018]

In a study of 173 patients with high-risk localized prostate cancer, long-term androgen deprivation therapy (ADT) for 36 months or more combined with external-beam radiotherapy (EBRT) significantly improved five-year progression-free survival rates (92.8%) compared to short-term ADT (72.9%).

Patients receiving short-term ADT experienced a higher incidence of cardiovascular toxicity (grade II or above) compared to those on long-term ADT, indicating that longer ADT may not only enhance survival but also have a more favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of the duration of hormonal therapy following radiotherapy for localized prostate cancer. Okubo, M., Nakayama, H., Itonaga, T., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Optimal Androgen Deprivation Therapy Combined with Proton Beam Therapy for Prostate Cancer: Results from a Multi-Institutional Study of the Japanese Radiation Oncology Study Group. [2020]

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

High-risk prostate cancer: combination of high-dose, high-precision radiotherapy and androgen deprivation therapy. [2021]

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

Assessing the Optimum Use of Androgen-Deprivation Therapy in High-Risk Prostate Cancer Patients Undergoing External Beam Radiation Therapy. [2022]

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

Excellent results from high dose rate brachytherapy and external beam for prostate cancer are not improved by androgen deprivation. [2022]

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

Radiation and hormonal therapy for locally advanced and clinically localized prostate cancer. [2019]

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

Combination of Radiation Therapy and Short-Term Androgen Blockade With Abiraterone Acetate Plus Prednisone for Men With High- and Intermediate-Risk Localized Prostate Cancer. [2021]

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

Variations in patterns of concurrent androgen deprivation therapy use based on dose escalation with external beam radiotherapy vs. brachytherapy boost for prostate cancer. [2019]

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

The use of Hormonal Therapy to Augment Radiation Therapy in Prostate Cancer: An Update. [2018]

9. Greece pubmed.ncbi.nlm.nih.gov

Impact of the duration of hormonal therapy following radiotherapy for localized prostate cancer. [2022]

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

Interplay Between Duration of Androgen Deprivation Therapy and External Beam Radiotherapy With or Without a Brachytherapy Boost for Optimal Treatment of High-risk Prostate Cancer: A Patient-Level Data Analysis of 3 Cohorts. [2023]