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

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to treating high-risk prostate cancer. Researchers aim to determine if a shorter course of hormone therapy (androgen deprivation therapy, or ADT) combined with two types of radiation can safely and effectively prevent the cancer from returning or spreading. Participants will receive hormone therapy, internal radiation (brachytherapy), and targeted external radiation over a few months. Men diagnosed with aggressive prostate cancer, as indicated by certain test results, might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer care.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In a previous study, androgen deprivation therapy (ADT) effectively controlled prostate cancer. It lowered prostate-specific antigen levels in over 90% of patients and reduced tumor size in 80% to 90% of cases. However, some studies suggest that ADT might increase the risk of heart problems, such as heart attacks.

Brachytherapy, which involves placing tiny radioactive seeds in the prostate, is generally considered safe according to studies. This treatment helps prevent cancer from spreading and is often used with other treatments for patients at high risk.

Research on hypofractionated external beam radiation therapy (a shorter, more intense schedule) shows it works well for high-risk prostate cancer. It has side effects related to urinary and bowel functions, but these are usually manageable.

Overall, these treatments have been well-studied and are considered safe. However, each treatment has possible side effects that should be discussed with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for high-risk prostate cancer because it combines a shorter course of hormone therapy with innovative radiation techniques. Unlike traditional treatments that often require longer hormone therapy, this approach uses androgen deprivation therapy for just six months. Additionally, it incorporates brachytherapy and hypofractionated radiation, which delivers higher doses of radiation in fewer sessions, potentially enhancing effectiveness while reducing treatment time. This combination aims to maximize cancer control while minimizing side effects and inconvenience for patients.

What evidence suggests that this trial's treatments could be effective for high-risk prostate cancer?

In this trial, participants will receive a combination of treatments. Research has shown that androgen deprivation therapy (ADT), one of the treatments in this trial, can help manage prostate cancer. ADT has improved survival rates, with some patients living more than six years on average. Studies also indicate that it can lower the risk of cancer progression over ten years.

Brachytherapy, another treatment option in this trial, involves placing tiny radioactive seeds in the prostate and has demonstrated high survival rates. Specifically, one study reported that 70% of certain patients were still alive 15 years after treatment.

Hypofractionated external beam radiation therapy, also part of this trial, uses higher doses of radiation in fewer sessions and has proven effective for high-risk prostate cancer. Research indicates that 82% of patients did not experience a return of cancer, remaining cancer-free. ^{2 3 6 7 8}

Who Is on the Research Team?

Daniel Gorovets, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0302283825004361

Short-term Androgen Deprivation Therapy and High-dose ... Among the 370 patients in the modified intention-to-treat population, 241 (65%) had intermediate-risk and 107 (28%) high-risk prostate cancer.

2. ascopubs.org ascopubs.org/doi/10.1200/EDBK_433126

Balancing Hormone Therapy: Mitigating Adverse Effects of ... Treatment advances including ADT have led to improvements in PCa management and survival, with trials reporting median survival of over 6 years ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4986307/

Evidence-based recommendations on androgen deprivation ... After a 10-year follow up period, a significant reduction in the risk of biochemical and local progression were observed in men treated with combination therapy ...

4. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2788324

Interplay Between Duration of Androgen Deprivation ... This cohort study explores associations between the duration of androgen deprivation therapy and distant metastasis-free survival in men ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10372191/

Effects of Androgen Deprivation Therapy on Prostate Cancer ... We analysed the effectiveness of androgen deprivation therapy (ADT) for localised prostate cancer among patients, defined by the relative risk (RR) for cancer ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4094624/

Androgen deprivation therapy for prostate cancer: long-term ... ADT can normalize serum prostate specific antigen in over 90% of patients and results in sizable tumor response in 80% to 90%. This treatment can be done either ...

7. ahajournals.org ahajournals.org/doi/10.1161/circulationaha.109.192695

Androgen-Deprivation Therapy in Prostate Cancer and ... Several studies have reported an association between ADT and an increased risk of cardiovascular events, including myocardial infarction and cardiovascular ...

8. cancer.gov cancer.gov/types/prostate/prostate-hormone-therapy-fact-sheet

Hormone Therapy for Prostate Cancer Fact Sheet - NCI Hormone therapies, which are treatments that decrease androgen levels or block androgen action, can inhibit the growth of such prostate cancers.