Antiandrogen Therapy + SBRT for Metastatic Prostate Cancer

Overseen By Vincent Basehart

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must be taking: Antiandrogens

Must not be taking: CYP3A4 inducers

Disqualifiers: Spinal cord compression, Prior pelvic malignancy, Concurrent malignancy, 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: Unknown

Duration: 6 months

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well antiandrogen therapy (leuprolide, apalutamide, and abiraterone acetate) and stereotactic body radiation therapy (SBRT) works in treating patients with prostate cancer that has come back and has spread to other parts of the body. Drugs used in chemotherapy, such as leuprolide, apalutamide, and abiraterone acetate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. SBRT uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving antiandrogen therapy and SBRT may work better in treating patients with prostate cancer.

Will I have to stop taking my current medications?

The trial requires that medications known to lower the seizure threshold be stopped or replaced at least 4 weeks before joining. Also, if you are taking strong CYP3A4 inducers, adjustments will be needed. Other medications may need to be adjusted, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Abiraterone Acetate (Zytiga) for treating metastatic prostate cancer?

Research shows that Abiraterone Acetate (Zytiga) improves overall survival in patients with metastatic castration-resistant prostate cancer, especially when used after chemotherapy with docetaxel. It has been shown to be more effective than prednisone in clinical trials. ^{1 2 3 4 5}

Is the combination of antiandrogen therapy and SBRT generally safe for humans?

Abiraterone acetate, used in combination with prednisone, has been shown to be generally safe for treating metastatic prostate cancer, with some side effects like low potassium levels, high blood pressure, fluid retention, and liver issues. Leuprolide acetate, another component, has also been studied for safety in prostate cancer treatment. While specific safety data for the combination with SBRT is not detailed, these components have been evaluated for safety in humans. ^{2 3 6 7 8}

How is the treatment of Antiandrogen Therapy + SBRT for Metastatic Prostate Cancer different from other treatments?

This treatment combines antiandrogen drugs like Abiraterone Acetate and Apalutamide with Stereotactic Body Radiation Therapy (SBRT), which is a precise form of radiation therapy. This combination aims to improve outcomes by targeting cancer cells more effectively than using hormone therapy or radiation alone. ^{3 4 8 9 10}

Research Team

Amar Kishan

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

Men with recurrent, metastatic prostate cancer after surgery are eligible for this trial if they have 1-5 visible metastases and no visceral spread. They must be fit enough for radiation therapy, have adequate blood counts and organ function, and not be on certain medications or have conditions that could cause seizures.

Inclusion Criteria

My cancer spread can be treated with targeted radiation.

Serum total bilirubin =< 1.5 x upper limits of normal (ULN)

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x ULN

Exclusion Criteria

I have a digestive condition that affects how my body absorbs food.

I have inflammatory bowel disease or an active connective tissue disorder.

I cannot have radiotherapy or hormone therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of leuprolide SC on day 1, and apalutamide and abiraterone acetate orally once daily for up to 6 months. SBRT is administered over 1, 3, or 5 fractions starting 2 months after initiation of ADT.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up visits within 2-4 weeks, every 30 days for 6 months, and then every 3 months thereafter.

Up to 2 years

Treatment Details

Interventions

• Abiraterone Acetate
• Apalutamide
• Leuprolide Acetate
• Stereotactic Body Radiation Therapy

Trial Overview The trial is testing a combination of antiandrogen drugs (leuprolide, apalutamide, abiraterone acetate) with high-precision radiation therapy called SBRT to see if it's more effective in treating prostate cancer that has returned and spread.

Participant Groups

Group I: Treatment (leuprolide, apalutamide, abiraterone acetate, SBRT) Experimental Treatment 6 Interventions

Patients receive leuprolide SC on day 1, Patients receive a single dose of leuprolide SC on day 1 and apalutamide PO QD and abiraterone acetate PO QD for up to 6 months in the absence of disease progression or unacceptable toxicity. Beginning 2 months of initiation of ADT, patients also receive SBRT over 1, 3, or 5 fractions in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Metastatic high-risk castration-sensitive prostate cancer

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Newly diagnosed high-risk metastatic hormone-sensitive prostate cancer

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Metastatic castration-sensitive prostate cancer

Approved in Japan as Zytiga for:

• Prostate cancer

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Janssen Inc.

Industry Sponsor

Trials

24

Recruited

8,100+

Findings from Research

A study of 368 patients with metastatic castration-resistant prostate cancer (mCRPC) found five key risk factors that can predict overall survival (OS) after starting abiraterone acetate treatment, including low hemoglobin levels and high number of metastases.

Using these risk factors, patients can be categorized into three groups based on their prognosis, with median survival times ranging from 22.6 months for those with fewer risk factors to just 6.2 months for those with more, helping guide treatment decisions and patient counseling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which Factors Predict Overall Survival in Patients With Metastatic Castration-Resistant Prostate Cancer Treated With Abiraterone Acetate Post-Docetaxel? Van Praet, C., Rottey, S., Van Hende, F., et al.[2018]

A study involving 32 healthy male subjects demonstrated that the test product (abiraterone acetate tablet) is bioequivalent to the reference product ZYTIGA® in terms of pharmacokinetics, with both products showing similar maximum concentration (Cmax) and area under the curve (AUC) values within the acceptable range.

The research confirmed significant intra-subject variability in the pharmacokinetics of abiraterone, indicating that individual responses to the drug can vary widely, which is important for clinicians to consider when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. Wang, C., Hu, C., Gao, D., et al.[2022]

In a Swedish observational study of 119 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate treatment resulted in similar overall survival rates compared to those seen in the pivotal clinical trial, despite a shorter median treatment duration of 5.6 months versus 7.3 months in the trial.

The findings suggest that while Swedish patients may have characteristics that could limit their treatment benefits, they still achieve comparable survival outcomes, indicating a potentially more cost-effective use of abiraterone in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value of treatment in clinical trials versus the real world: the case of abiraterone acetate (Zytiga) for postchemotherapy metastatic castration-resistant prostate cancer patients in Sweden. Svensson, J., Andersson, E., Persson, U., et al.[2017]

In a study involving 1919 patients with metastatic prostate cancer, the addition of abiraterone acetate to standard androgen deprivation therapy significantly improved overall survival, with a median survival of 76.6 months compared to 45.7 months for standard care alone.

Combining both abiraterone and enzalutamide did not provide additional survival benefits over abiraterone alone, and it was associated with higher rates of severe side effects, suggesting that this combination should be avoided in long-term treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. Attard, G., Murphy, L., Clarke, NW., et al.[2023]

In a study of 58 elderly patients with metastatic castration-resistant prostate cancer (mCRPC), non-adherence rates to the treatments abiraterone and enzalutamide were low at 4.8% overall, indicating good adherence among this population.

Non-adherence was linked to patients' frailty and their radiological response to treatment, suggesting that geriatric assessments could help identify at-risk patients and improve adherence to these important cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to abiraterone or enzalutamide in elderly metastatic castration-resistant prostate cancer. Banna, GL., Urzia, V., Benanti, C., et al.[2021]

In a 6-month study involving 117 patients with prostate cancer, the 3-month subcutaneous depot of leuprolide acetate (LA-2550) effectively suppressed serum testosterone levels to below 50 ng/dl in 98% of patients by day 28, and all patients achieved this level by day 35.

The treatment was well-tolerated, with no flare reactions and minimal adverse effects, primarily mild to moderate hot flashes, indicating a favorable safety profile while achieving significant reductions in testosterone and prostate-specific antigen levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical study of 22.5 mg. La-2550: A new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer. Chu, FM., Jayson, M., Dineen, MK., et al.[2023]

Abiraterone acetate significantly improves overall survival and radiographic progression-free survival in men with metastatic castration-resistant prostate cancer (CRPC) when combined with prednisone, based on results from a multinational phase III study involving men who had previously received docetaxel.

The treatment is generally well-tolerated, although it can cause side effects like hypokalaemia and hypertension; however, serious adverse events were relatively low in the phase III studies, indicating it is a viable option for managing metastatic CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a review of its use in patients with metastatic castration-resistant prostate cancer. Hoy, SM.[2021]

Oral abiraterone acetate (Zytiga®) significantly improves overall survival and progression-free survival in patients with metastatic castration-resistant prostate cancer (CRPC) when used with prednisone, compared to a placebo.

The treatment is specifically effective for patients who have already undergone docetaxel-containing chemotherapy, highlighting its role as a subsequent therapy in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. Scott, LJ., Yang, LPH., Lyseng-Williamson, KA.[2021]

Abiraterone acetate combined with prednisone significantly improves overall survival (34.7 months vs 30.3 months) and radiologic progression-free survival (16.5 months vs 8.3 months) in patients with metastatic castration-resistant prostate cancer compared to placebo.

The treatment is generally well-tolerated, with manageable side effects primarily related to mineral corticoid excess, and it also enhances the perceived quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Abiraterone in castration resistant prostate cancer.] Juárez Soto, A., Caballero Cobos, R., Campanario Pérez, R., et al.[2018]

References

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

Which Factors Predict Overall Survival in Patients With Metastatic Castration-Resistant Prostate Cancer Treated With Abiraterone Acetate Post-Docetaxel? [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. [2022]

3. Sweden pubmed.ncbi.nlm.nih.gov

Value of treatment in clinical trials versus the real world: the case of abiraterone acetate (Zytiga) for postchemotherapy metastatic castration-resistant prostate cancer patients in Sweden. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Adherence to abiraterone or enzalutamide in elderly metastatic castration-resistant prostate cancer. [2021]

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

A clinical study of 22.5 mg. La-2550: A new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer. [2023]

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

Abiraterone acetate: a review of its use in patients with metastatic castration-resistant prostate cancer. [2021]

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

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021]

9. Spain pubmed.ncbi.nlm.nih.gov

[Abiraterone in castration resistant prostate cancer.] [2018]

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

A territory-wide real-world efficacy and toxicity analysis of abiraterone acetate versus docetaxel in 574 Asian patients with metastatic hormone-sensitive prostate cancer. [2023]