Hormone Therapy + SBRT + Enzalutamide for Prostate Cancer

(PCS IX Trial)

Recruiting at 10 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

102 Participants Needed

Trial Summary

What is the purpose of this trial?

This adaptive phase II/III randomized trial is designed to demonstrate that eradication of oligometastases by SBRT is a promising and emerging way to delay disease progression and postpone second line systemic therapies in castration-resistant prostate cancer (CRPC) patients. Only CRPC patients with an oligometastatic recurrence will be eligible to take part in this trial. All participating patients will receive either the standard of care (i.e. LHRH agonist in combination with the new generation of hormonal therapy \[Enzalutamide\]) or the experimental treatment (i.e. LHRH agonist in combination with the new generation of HT \[Enzalutamide\] plus the additional SBRT treatment). The patients will undergo different evaluations before treatment, such as imaging to confirm oligometastatic recurrence and blood tests. Patients will be stratified according to the location of metastasis (visceral \[with or without bone metastases\] vs. bone metastases alone) and PSA doubling time (≤ 3 vs. \> 3 months). As per the standard of care, patients will have PSA testing performed every 6-12 weeks and re-imaging at 6, 9, 12, 18 and 24 months or at PSA progression, whichever occurs first.

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.

What data supports the effectiveness of the drug Enzalutamide for prostate cancer?

Research shows that Enzalutamide is effective for patients with metastatic castration-resistant prostate cancer, as it is FDA-approved for this condition. Additionally, a case study reported that a patient who progressed on Enzalutamide achieved complete remission after receiving stereotactic body radiation therapy, suggesting potential benefits of combining these treatments. ^{1 2 3 4 5}

Is the combination of hormone therapy, SBRT, and Enzalutamide safe for prostate cancer treatment?

Research shows that hormone therapies like leuprolide acetate and goserelin acetate are generally safe for prostate cancer treatment, with common side effects including hot flashes. These treatments have been well-tolerated in various studies, suggesting they are safe for use in humans. ^{4 6 7 8 9}

How is the treatment with Enzalutamide, Goserelin Acetate, Leuprolide Acetate, and Stereotactic Body Radiation Therapy unique for prostate cancer?

This treatment combines hormone therapy with advanced radiation techniques and a novel drug, Enzalutamide, which blocks the effects of male hormones that fuel prostate cancer growth. This multi-faceted approach aims to improve outcomes by targeting the cancer from different angles, potentially offering better control over the disease compared to traditional treatments. ^{10 11 12 13 14}

Research Team

Dr. Tamim Niazi, MDCM

Principal Investigator

Jewish General Hospital

Eligibility Criteria

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

My condition is worsening despite treatment.

I have not had chemotherapy for prostate cancer.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Enzalutamide for patients with metastatic castration-resistant prostate cancer. [2020]

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

Eligard: leuprolide acetate in a novel sustained-release delivery system. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for the treatment of oligoprogression on androgen receptor targeted therapy in castration-resistant prostate cancer. [2020]

4. Switzerland 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. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Phase II open-label study investigating apalutamide in patients with biochemical progression after radical prostatectomy. [2021]

6. New Zealand pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Safety and clinical efficacy of a new 6-month depot formulation of leuprorelin acetate in patients with prostate cancer in Europe. [2022]

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

Comparison of tolerability and adverse events following treatment with two GnRH agonists in patients with advanced prostate cancer. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Endocrine effects, efficacy and tolerability of a 10.8-mg depot formulation of goserelin acetate administered every 13 weeks to patients with advanced prostate cancer. [2019]

10. China pubmed.ncbi.nlm.nih.gov

From bench to bedside: bipolar androgen therapy in a pilot clinical study. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Goserelin acetate in combination with radiotherapy for prostate cancer. [2019]

12. Japan pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and safety of 1- and 3-month luteinizing hormone-releasing hormone agonist depots as initial therapies for prostate cancer. [2021]

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

Comparison of goserelin and leuprolide in combined androgen blockade therapy. [2022]

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

Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. [2022]