ARN-509 +/− Abiraterone for Prostate Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a combination of treatments for high-risk prostate cancer, aiming to slow or stop the cancer's growth. The focus is on using a mix of medications, including ARN-509 (an anti-androgen drug) and abiraterone (also known as Zytiga, which lowers androgen levels), to reduce androgen—a hormone that can fuel cancer growth—and improve outcomes before surgery. Participants will be divided into groups, with some receiving different combinations of these treatments and others undergoing surgery alone. The trial seeks men diagnosed with aggressive prostate cancer or those with high levels of prostate-specific antigen (PSA), whose cancer can be surgically removed. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that ARN-509, also known as apalutamide, is generally safe and well tolerated. Studies have found it effective in treating prostate cancer, with many patients continuing treatment without serious side effects. For instance, in previous studies, 80% of patients who hadn't used certain prior treatments remained on ARN-509 without major issues.

When combined with abiraterone acetate, GnRH agonists, and prednisone, ARN-509 shows encouraging safety results. The FDA has already approved abiraterone acetate with prednisone for treating prostate cancer, indicating its safety under certain conditions. This combination has been studied for its ability to manage prostate cancer by reducing androgen levels, which can promote cancer growth.

Overall, existing evidence supports that both ARN-509 alone and in combination with other drugs are well tolerated by patients. However, as with any treatment, individual experiences may vary, so discussing potential side effects with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they offer innovative approaches compared to traditional options like surgery and hormone therapy. ARN-509 is an androgen receptor antagonist that specifically targets and blocks the receptors that fuel prostate cancer growth, which could make it more effective at slowing down the disease. When combined with abiraterone acetate, which reduces androgen production, and a GnRH analog, this approach tackles the cancer on multiple fronts, potentially improving outcomes. The addition of prednisone helps manage side effects, making the treatment more tolerable. These combined strategies could offer a more comprehensive attack on prostate cancer, promising better control over disease progression.

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

This trial will compare different treatment approaches for prostate cancer. Studies have shown that ARN-509, also known as apalutamide, effectively treats prostate cancer by blocking androgen receptors, which helps stop cancer cell growth. In this trial, some participants will receive ARN-509 alone, while others will receive it with hormone therapy, including abiraterone acetate and a GnRH agonist. Research indicates that combining ARN-509 with these hormone therapies can reduce male hormone levels that promote prostate cancer growth, potentially improving survival rates and tumor control. Prednisone, another part of the combination treatment, may help kill cancer cells or stop them from multiplying. Overall, these combined medications could be more effective in managing prostate cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Saum Ghodoussipour, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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 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®) 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]

Citations

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Survival outcomes of apalutamide as a starting treatment Starting treatment with APA + ADT was associated with a significantly reduced risk of death compared with ENZ + ADT (aHR, 95%CI) (0.66, 0.51– ...

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Safety and Antitumor Activity of Apalutamide (ARN-509) in ... All received apalutamide 240 mg/day. Primary endpoint was ≥50% decline in 12-week PSA according to Prostate Cancer Working Group 2 criteria. Secondary endpoints ...

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Efficacy | ERLEADA® (apalutamide) HCP Median follow-up time was 44.0 months. 1. The survival rate at 48 months was 65.1% for ERLEADA ® + ADT patients vs 51.8% for placebo + ADT patients.

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Safety and Antitumor Activity of Apalutamide (ARN-509) in ... This study addressed the effect of activity of apalutamide in metastatic castration-resistant prostate cancer patients who were naïve to prior abiraterone plus ...

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Study Results | Safety, Pharmacokinetic and Proof-of- ... Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 (Apalutamide) in Castration-Resistant Prostate Cancer (CRPC). ClinicalTrials.gov ID NCT01171898.