Hormone Therapy + SBRT + Enzalutamide for Prostate Cancer

(PCS IX Trial)

Not currently recruiting at 11 trial locations

Overseen By Ashley Feng, M.Sc

Age: 18+

Sex: Male

Trial Phase: Phase 2 & 3

Sponsor: Sir Mortimer B. Davis - Jewish General Hospital

Must be taking: LHRH agonist

Must not be taking: Opiate analgesics, Herbal products

Disqualifiers: Brain metastasis, Seizure history, 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: 7

Duration: 6-12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach for managing castration-resistant prostate cancer (CRPC) that has spread to a limited number of areas, known as oligometastases. The study compares standard hormone therapy with an additional treatment, stereotactic body radiation therapy (SBRT), to determine if it can delay disease progression and postpone more aggressive treatments. Men with CRPC who are already on hormone therapy and have a few small cancer spots not previously treated with radiation may be suitable candidates for this trial. The trial also includes Enzalutamide, a medication that blocks the effects of androgens (male hormones) that can promote tumor growth. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering a chance to advance prostate cancer treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before enrolling. Specifically, you must stop taking flutamide, bicalutamide, nilutamide, 5-α reductase inhibitors, estrogens, cyproterone, systemic biologic therapy for prostate cancer, investigational agents, and certain herbal products at least 4-6 weeks before starting the trial.

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

Research has shown that hormone therapy with enzalutamide is generally well-tolerated. When combined with LHRH agonists (another type of hormone therapy), enzalutamide has a safety profile similar to other hormone treatments. Common side effects include hot flashes and fatigue. However, enzalutamide may increase the risk of heart problems, such as heart failure and high blood pressure.

Studies suggest that Stereotactic Body Radiation Therapy (SBRT) is safe and practical for patients with prostate cancer, particularly when the cancer is localized. SBRT is a precise form of radiation therapy that targets cancer while sparing most surrounding healthy tissue.

Overall, research supports the safety of these treatments, but discussing any concerns with a healthcare professional before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of hormone therapy, SBRT, and enzalutamide for prostate cancer because it offers a multi-faceted approach that could enhance treatment effectiveness. Unlike conventional hormone therapies that primarily use LHRH agonists like goserelin or leuprolide acetate, this treatment adds enzalutamide, a next-generation hormonal therapy that blocks androgen receptors more effectively. Additionally, the inclusion of Stereotactic Body Radiation Therapy (SBRT) offers precise, high-dose radiation targeting that may improve outcomes by focusing on cancer cells while minimizing damage to surrounding tissues. This combination aims to provide a powerful one-two punch against prostate cancer, potentially leading to better patient outcomes.

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

In this trial, participants will receive either a combination of enzalutamide with LHRH agonists or the same combination plus SBRT. Previous studies have shown that combining enzalutamide with LHRH agonists helps prostate cancer patients live longer. Enzalutamide blocks male hormones that can promote cancer growth. Research also indicates that adding SBRT, a precise type of radiation therapy, to hormone treatment can slow the progression of prostate cancer that no longer responds to standard hormone therapy. SBRT targets small areas where cancer has spread, potentially delaying the need for more intense treatments. Overall, this combination aims to manage this type of prostate cancer more effectively, extending periods without disease progression. ^{2 4 6 7 8}

Who Is on the Research Team?

Dr. Tamim Niazi, MDCM

Principal Investigator

Jewish General Hospital

Are You a Good Fit for This Trial?

Men aged 18+ with castration-resistant prostate cancer and oligometastatic recurrence, who are on or will continue androgen deprivation therapy. They must have a low testosterone level, up to 5 metastases amenable to SBRT, no prior chemotherapy for prostate cancer, an ECOG performance status of 0-2 or Karnofsky >70%, and agree to use contraception. Exclusions include severe cardiovascular conditions, recent seizures or strokes, certain blood pressure levels, absorption disorders, recent major surgery or opiate analgesic use.

Inclusion Criteria

Estimated life expectancy of ≥ 6 months

Patients and their female partners of childbearing potential must be willing to use two forms of contraception throughout the study and for 3 months after the last dose of study drug

My condition is worsening despite treatment.

Exclusion Criteria

I have not been excluded due to previous treatments.

I have received radiation therapy for cancer spread.

Severe concurrent disease, infection, or co-morbidity that would make the patient inappropriate for enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either standard of care with LHRH agonist and Enzalutamide or experimental treatment with additional SBRT

6-12 weeks

Multiple visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including PSA testing and re-imaging

5 years

PSA testing every 6-12 weeks, re-imaging at 6, 9, 12, 18, and 24 months

Long-term Follow-up

Participants are monitored for long-term outcomes such as overall survival and quality of life

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• Goserelin Acetate
• Leuprolide Acetate
• Stereotactic Body Radiation Therapy
• Triptorelin

Trial Overview This trial is testing whether adding Stereotactic Body Radiation Therapy (SBRT) to the standard care (LHRH agonist plus Enzalutamide) can delay disease progression in men with oligometastatic castration-resistant prostate cancer. Participants will be randomly assigned to receive either the standard treatment alone or combined with SBRT.

How Is the Trial Designed?

Group I: LHRH agonist + Enzalutamide + SBRT Experimental Treatment 5 Interventions

Subjects will receive LHRH agonist in combination with the new generation of hormone therapy (enzalutamide, 40mg) plus the additional SBRT treatment

Group II: LHRH agonist + Enzalutamide Active Control 4 Interventions

Subjects will receive LHRH agonist in combination with the new generation of hormonal therapy (enzalutamide, 40mg)

Enzalutamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in European Union as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Canada as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Japan as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Who Is Running the Clinical Trial?

Sir Mortimer B. Davis - Jewish General Hospital

Lead Sponsor

Trials

61

Recruited

25,800+

Published Research Related to This Trial

Enzalutamide is an effective androgen receptor inhibitor that improves overall survival in patients with metastatic castration-resistant prostate cancer, showing a 4.8-month survival benefit in those previously treated with docetaxel, as demonstrated in the Phase III AFFIRM trial.

The FDA has expanded enzalutamide's approval to include first-line treatment for metastatic castration-resistant prostate cancer in patients who have not yet received chemotherapy, and it is associated with an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide for patients with metastatic castration-resistant prostate cancer. Ramadan, WH., Kabbara, WK., Al Basiouni Al Masri, HS.[2020]

The SAVE trial is a Phase II study involving 202 men with advanced prostate cancer, comparing the effects of apalutamide combined with salvage radiotherapy against androgen-deprivation therapy plus salvage radiotherapy.

The primary goal is to evaluate sexual function after nine months of treatment, while also assessing quality of life, safety, and short-term efficacy of apalutamide, highlighting its potential benefits in managing prostate cancer post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II open-label study investigating apalutamide in patients with biochemical progression after radical prostatectomy. Dirix, P., Strijbos, M., den Mooter, TV., et al.[2021]

In a study involving 1,906 patients with advanced prostate cancer, both 3-month and 6-month leuprorelin acetate depot formulations significantly reduced prostate-specific antigen (PSA) levels from an average of 12.0 ng/mL to 0.5 ng/mL after 12 months, indicating effective treatment.

The treatment was well-tolerated, with only 8.8% of patients experiencing adverse events, suggesting that leuprorelin acetate is a safe option for managing advanced prostate cancer in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Leuprorelin Acetate (Eligard®) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer. Ohlmann, CH., Gross-Langenhoff, M.[2018]

A case study of a patient with castration-resistant prostate cancer showed that combining ablative stereotactic body radiation therapy with ongoing enzalutamide treatment resulted in a durable complete remission, despite prior progression on the medication.

This finding highlights the potential for innovative treatment strategies in advanced prostate cancer and suggests the need for further clinical trials to explore this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for the treatment of oligoprogression on androgen receptor targeted therapy in castration-resistant prostate cancer. Nguyen, TC., Bajwa, R., Bari, S., et al.[2020]

The 6-month GnRH agonist depot formulations, leuprolide acetate 45 mg and triptorelin pamoate 22.5 mg, are effective for palliative treatment of advanced prostate cancer, achieving chemical castration rates of 93% to 99%, while also improving patient convenience by reducing the frequency of injections.

Both formulations have a safety profile similar to existing treatments, with hot flashes being the most common side effect, suggesting they can be effectively integrated with other cancer treatments like surgery and chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Six-month gonadotropin releasing hormone (GnRH) agonist depots provide efficacy, safety, convenience, and comfort. Crawford, ED., Phillips, JM.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11667785/

Luteinizing hormone-releasing hormone receptor agonists ... LHRH-R agonists and antagonists, particularly goserelin, have demonstrated long-term survival benefits in patients with localized and locally advanced prostate ...

2. openurologyandnephrologyjournal.com openurologyandnephrologyjournal.com/VOLUME/17/ELOCATOR/e1874303X237036/FULLTEXT/

6-month Formulations of Androgen Deprivation Therapy for ... A recent analysis found a high non-adherence rate of 84% for LHRH agonist injections based on dosing schedules used in pivotal trials. Method:.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02023463?tab=table

Enzalutamide, Radiation Therapy and Hormone ... To determine the efficacy of the combination of enzalutamide with an LHRH agonist and radiation therapy using PSA nadir. To describe patient-reported outcomes ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4939158/

An Update on Triptorelin: Current Thinking on Androgen ... In the largest of these studies, castrate levels of testosterone were reached after 28 days in 91.2% of 140 men randomized to treatment with the triptorelin ...

5. cancerbiomed.org cancerbiomed.org/content/21/11/1012.abstract

effects on long-term survival and combined therapy with ... LHRH-R agonists and antagonists, particularly goserelin, have demonstrated long-term survival benefits in patients with localized and locally advanced prostate ...

6. nature.com nature.com/articles/s41391-018-0079-0

Androgen-targeted therapy in men with prostate cancer The safety profiles of the LHRH agonists are similar and they are generally well tolerated. The most common adverse effects (AE) are hot ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39718161/

effects on long-term survival and combined therapy with ... LHRH-R agonists and antagonists, particularly goserelin, have demonstrated long-term survival benefits in patients with localized and locally ...

8. mdpi.com mdpi.com/2813-0618/3/4/26

Cardiovascular Adverse Events Associated with Prostate ... Among the antiandrogens, enzalutamide lowers MI, CAD, and angina risks but raises the risks of heart failure and hypertension. In contrast, bicalutamide is ...