ARN-509 +/− Abiraterone for Prostate Cancer

Recruiting at 1 trial location

Age: Any Age

Sex: Male

Trial Phase: Phase 2

Sponsor: Rutgers, The State University of New Jersey

Must be taking: Androgen receptor antagonists

Must not be taking: Seizure threshold lowering drugs

Disqualifiers: Seizure history, Metastatic cancer, 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: 3 months

90 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications known to lower the seizure threshold at least 4 weeks before joining the study. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Abiraterone Acetate in combination with prednisone for prostate cancer?

Research shows that Abiraterone Acetate, when used with prednisone, significantly improves survival in patients with metastatic castration-resistant prostate cancer. Clinical trials have demonstrated that this combination prolongs overall survival and delays disease progression compared to a placebo. ^{1 2 3 4 5}

What safety information is available for the use of LHRH analogues and Abiraterone in prostate cancer treatment?

LHRH analogues like goserelin and leuprorelin are generally safe but can cause side effects such as hot flushes, loss of libido, and skin reactions at the injection site. Rarely, they may cause severe allergic reactions (anaphylaxis), so patients should be monitored carefully. ^{6 7 8 9 10}

What makes the drug combination of ARN-509 and Abiraterone Acetate unique for prostate cancer treatment?

The drug combination of ARN-509 and Abiraterone Acetate is unique because it targets prostate cancer by inhibiting testosterone synthesis and androgen receptor signaling, which are crucial for cancer growth. This combination is particularly used for metastatic castration-resistant prostate cancer, offering a novel approach by combining two mechanisms to potentially improve treatment outcomes. ^{1 2 5 11 12}

What is the purpose of this trial?

This randomized phase II trial studies how well androgen receptor antagonist ARN-509 works with or without abiraterone acetate, gonadotropin-releasing hormone agonist, and prednisone in treating patients with high-risk prostate cancer undergoing surgery. Androgen can cause the growth of prostate cancer cells. Hormone therapy using androgen receptor antagonist ARN-509, abiraterone acetate, and gonadotropin-releasing hormone analog (GnRH agonist) may fight prostate cancer by lowering the levels of androgen the body makes. Prednisone may either kill the tumor cells or stop them from dividing. Giving androgen receptor agonist ARN-509 with or without abiraterone acetate, GnRH agonist and prednisone may work better in treating patients with prostate cancer.

Research Team

Saum Ghodoussipour, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Eligibility Criteria

Men with high-risk prostate cancer who are planning to undergo surgery can join. They must have a Gleason score >8 or PSA >20, be in good physical condition (ECOG PS 0 or 1), and have no metastatic cancer or severe heart conditions. Their blood counts and organ functions need to meet specific levels, they should not be on seizure threshold-lowering meds for at least 4 weeks before the trial, and agree to use effective contraception.

Inclusion Criteria

Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry

Patients with Eastern Cooperative Oncology Group performance scale (ECOG PS) 0 or 1

Clinical stage T3 or less as demonstrated by abdominal/pelvic computed tomography (CT) or magnetic resonance imaging (MRI) will be selected as the prostate is resectable

Exclusion Criteria

Clinically significant ventricular arrhythmias within 6 months prior to randomization

Metastatic prostate cancer

Baseline moderate or severe hepatic impairment (Child-Pugh class B or C)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive androgen receptor antagonist ARN-509 with or without abiraterone acetate, GnRH agonist, and prednisone for 3 months, followed by radical prostatectomy

3 months

Surgery

Patients undergo radical prostatectomy

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Abiraterone Acetate
• ARN-509
• Gonadotropin-releasing Hormone Analog
• Prednisone

Trial Overview The trial is testing if ARN-509 works better alone or with abiraterone acetate, GnRH agonist, and prednisone in treating prostate cancer before surgery. The goal is to see if these treatments can reduce the amount of androgen since it helps prostate cancer cells grow.

Participant Groups

Group I: Arm I (androgen receptor ARN-509, radical prostatectomy) Experimental Treatment 4 Interventions

Patients receive androgen receptor antagonist ARN-509 PO daily for 3 months. Patients then undergo radical prostatectomy.

Group II: Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP) Active Control 7 Interventions

Patients receive GnRH agonist SC on day 1, androgen receptor antagonist ARN-509 PO daily PO for 4 times, abiraterone acetate PO daily for 4 times, and prednisone PO daily for 3 months. Patients then undergo radical prostatectomy.

Group III: Arm III (radical prostatectomy) Active Control 3 Interventions

Patients undergo radical prostatectomy.

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?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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, in combination with prednisone, received full FDA approval for treating metastatic castration-resistant prostate cancer (mCRPC) based on the COU-AA-302 trial, which involved 1,088 patients and showed a significant improvement in radiographic progression-free survival (rPFS) compared to placebo (8.3 months vs. not reached).

The trial also indicated a favorable trend in overall survival (OS) for patients receiving abiraterone acetate, although it did not reach statistical significance, confirming the drug's efficacy and safety profile consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. Kluetz, PG., Ning, YM., Maher, VE., et al.[2018]

In a study of 254 metastatic castration-resistant prostate cancer patients treated with abiraterone acetate plus prednisone (AA+P) over a median follow-up of 67.1 weeks, patient-reported outcomes (PROs) showed no significant decline in quality of life or cognitive function, indicating that the treatment is well-tolerated.

The study also reported a 66.4% response rate in prostate-specific antigen (PSA) levels, demonstrating the efficacy of AA+P in managing this patient population while maintaining their overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence in patient-reported outcomes (PROs) of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate + prednisone (AA+P) across Canada: Final results of COSMiC. Gotto, G., Drachenberg, DE., Chin, J., et al.[2020]

Oral abiraterone acetate (Zytiga®) effectively inhibits androgen biosynthesis, which is crucial for the progression of metastatic castration-resistant prostate cancer (mCRPC), and has been shown to prolong overall survival and radiographic progression-free survival in large phase 3 trials.

In combination with prednisone, abiraterone acetate has a manageable safety profile and is a convenient once-daily treatment option, making it a significant first-line therapy for men with mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone Acetate: A Review in Metastatic Castration-Resistant Prostrate Cancer. Scott, LJ.[2019]

In a study of 159 metastatic castration-resistant prostate cancer (mCRPC) patients, early-onset therapy with abiraterone acetate plus prednisone (AA + P) showed a median overall survival of 22.3 months, while late-onset therapy had a median overall survival of 39.2 months, indicating that timing of treatment may impact survival outcomes.

The treatment was generally well tolerated, with low incidence of serious adverse events (SAEs) reported, suggesting that AA + P is a safe option for mCRPC patients in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Early- vs. late-onset treatment using abiraterone acetate plus prednisone in chemo-naïve, asymptomatic or mildly symptomatic patients with metastatic CRPC after androgen deprivation therapy]. Merseburger, AS., Rüssel, C., Belz, H., et al.[2022]

In a study involving 2267 patients with metastatic castration-resistant prostate cancer, long-term use of low-dose prednisone (5mg twice daily) with or without abiraterone acetate resulted in a low incidence of corticosteroid-associated adverse events (CA-AEs), with only 25% of patients experiencing any grade CA-AEs.

The most common CA-AEs were hyperglycemia and weight increase, but the overall frequency of these events did not increase with longer exposure to prednisone, indicating that the treatment is safe and tolerable over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Incidence of Corticosteroid-associated Adverse Events on Long-term Exposure to Low-dose Prednisone Given with Abiraterone Acetate to Patients with Metastatic Castration-resistant Prostate Cancer. Fizazi, K., Chi, KN., de Bono, JS., et al.[2022]

In a phase II study involving 41 men with metastatic castration-resistant prostate cancer, increasing the dose of abiraterone acetate from 1000 mg to 2000 mg daily did not result in any significant clinical benefit, as no patients showed a prostate-specific antigen (PSA) decline of 30% or more after 12 weeks.

The study found that factors such as lower baseline circulating androgen levels and individual differences in drug metabolism may contribute to resistance against standard-dose abiraterone therapy, suggesting that simply increasing the dose is not an effective strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer. Friedlander, TW., Graff, JN., Zejnullahu, K., et al.[2018]

References

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

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

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

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. [2018]

3. Canada pubmed.ncbi.nlm.nih.gov

Real-world evidence in patient-reported outcomes (PROs) of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate + prednisone (AA+P) across Canada: Final results of COSMiC. [2020]

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

Abiraterone Acetate: A Review in Metastatic Castration-Resistant Prostrate Cancer. [2019]

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

[Early- vs. late-onset treatment using abiraterone acetate plus prednisone in chemo-naïve, asymptomatic or mildly symptomatic patients with metastatic CRPC after androgen deprivation therapy]. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Luteinising hormone releasing hormone analogues in the treatment of prostate cancer. [2019]

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

Randomised crossover trial to assess the tolerability of LHRH analogue administration. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

[Skin reaction induced by subcutaneous injection of LH-RH analogue]. [2013]

9. Australia pubmed.ncbi.nlm.nih.gov

Life-threatening anaphylaxis to leuprorelin acetate depot: case report and review of the literature. [2013]

10. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[APPLICATION OF DIFERELIN AND ITS PERSPECTIVES]. [2018]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Low Incidence of Corticosteroid-associated Adverse Events on Long-term Exposure to Low-dose Prednisone Given with Abiraterone Acetate to Patients with Metastatic Castration-resistant Prostate Cancer. [2022]

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

High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer. [2018]