Apalutamide for Prostate Cancer

Recruiting at 14 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Aragon Pharmaceuticals, Inc.

Must be taking: GnRH analogues

Must not be taking: Corticosteroids, Seizure potential

Disqualifiers: Metastases, Seizure history, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

127 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are currently taking corticosteroids, you will need to gradually stop taking them as soon as possible. Additionally, you cannot be on medications known to have seizure potential.

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

Apalutamide has been shown to significantly increase the time patients live without their cancer spreading in those with nonmetastatic castration-resistant prostate cancer, especially in those at high risk of developing metastases. Clinical trials, like the SPARTAN trial, demonstrated that Apalutamide improved metastasis-free survival and delayed the time to symptoms worsening, leading to its approval by the US FDA. ^{1 2 3 4 5}

Is apalutamide safe for humans?

Apalutamide is generally considered safe for humans, but it can cause side effects, with skin reactions being among the most common. It has been studied in patients with prostate cancer, and dose adjustments may help manage these side effects. ^{2 4 6 7 8}

What makes the drug Apalutamide unique for prostate cancer treatment?

Apalutamide is unique because it is a next-generation androgen receptor inhibitor specifically designed to treat castration-resistant prostate cancer by preventing the androgen receptor from entering the cell nucleus and activating cancer cell growth. It has shown significant benefits in delaying metastasis in patients with nonmetastatic castration-resistant prostate cancer, especially those at high risk of developing metastasis. ^{3 4 5 9 10}

What is the purpose of this trial?

The purpose of this study is to assess the safety and activity of ARN-509 in men with advanced castration resistant prostate cancer. Patients will first be enrolled into Phase 1 of the study to identify a tolerable dose for the Phase 2 portion of the study. In the Phase 2, 3 different cohorts of patients will be enrolled to evaluate the safety and activity of ARN-509.

Research Team

Aragon Pharmaceuticals, Inc Clinical Trial

Principal Investigator

Aragon Pharmaceuticals, Inc.

Eligibility Criteria

Men with advanced prostate cancer that hasn't spread far, who are on hormone therapy or have had surgery to lower testosterone levels. They should have a rising PSA level or a fast-doubling time for PSA, be fairly active (ECOG 0-1), and expected to live at least 3 more months. Men can't join if they've taken certain drugs like MDV3100 or ketoconazole, have heart issues (QTc > 450 msec), uncontrolled diseases, HIV, brain metastases, been treated with abiraterone, or have seizure risks.

Inclusion Criteria

I have been treated with abiraterone for at least 6 months before my disease got worse.

I am fully active or can carry out light work.

My prostate cancer is worsening, shown by tests or scans.

Exclusion Criteria

My cancer has spread to distant parts of my body, including the brain or spine.

I have been treated with abiraterone before.

I have been treated with ketoconazole before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation

ARN-509 is administered at escalating doses to determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

12 weeks

Phase 2: Treatment

Participants are divided into 3 cohorts to evaluate the safety and activity of ARN-509 at the RP2D

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 7 years

Treatment Details

Interventions

• ARN-509

Trial Overview The trial is testing ARN-509's safety and effectiveness in two phases for castration-resistant prostate cancer. Phase 1 finds the right dose; Phase 2 tests this dose further in different groups of patients to see how well it works and monitors safety.

Participant Groups

Group I: Treatment-naive metastatic CRPC (Phase 2) Experimental Treatment 1 Intervention

Participants with treatment-naive metastatic CRPC will be enrolled. ARN-509 will be administered at MTD and/or RP2D, determined in Phase 1.

Group II: Post-abiraterone metastatic CRPC (Phase 2) Experimental Treatment 1 Intervention

Participants with metastatic CRPC that are chemotherapy-naive, but have been previously treated with abiraterone will be enrolled. ARN-509 will be administered at MTD and/or RP2D, determined in Phase 1.

Group III: Non-metastatic CRPC (Phase 2) Experimental Treatment 1 Intervention

Participants with non-metastatic, treatment-naive Castration-Resistant Prostate Cancer (CRPC) with rapidly rising Prostate Specific Antigen (PSA) will be enrolled. ARN-509 will be administered at Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D), determined in Phase 1.

Group IV: Dose Escalation Cohort (Phase 1) Experimental Treatment 1 Intervention

ARN-509 will be administered at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily. Once Recommended Phase 2 Dose (RP2D) has been selected, Phase 1 participants being treated at the lower dose levels will be allowed to escalate to the RP2D level at the discretion of the primary investigator.

Who Is Running the Clinical Trial?

Aragon Pharmaceuticals, Inc.

Lead Sponsor

Trials

17

Recruited

5,400+

Findings from Research

In a study involving 55 Japanese patients with nonmetastatic castration-resistant prostate cancer, apalutamide combined with ongoing androgen deprivation therapy significantly improved metastasis-free survival compared to placebo, with median MFS not reached in the apalutamide group versus 18.23 months in the placebo group.

The safety profile of apalutamide was similar to that observed in the global population, with no new safety concerns identified, indicating that it is a safe and effective treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of apalutamide in Japanese patients with nonmetastatic castration-resistant prostate cancer: a subgroup analysis of a randomized, double-blind, placebo-controlled, Phase-3 study. Uemura, H., Satoh, T., Tsumura, H., et al.[2022]

In a study involving 57 patients with metastatic castration-resistant prostate cancer (mCRPC), the combination of apalutamide with abiraterone acetate and prednisone was well tolerated and demonstrated significant antitumor activity, particularly in patients who had not previously been treated with androgen receptor inhibitors.

While apalutamide reduced the systemic exposure to prednisone by 61%, no significant adverse events related to mineralocorticoid excess were observed, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Antitumor Effect of Apalutamide with Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer: Phase Ib Study. Posadas, EM., Chi, KN., de Wit, R., et al.[2021]

In a study of 107 patients with advanced prostate cancer, reducing the dose of apalutamide did not significantly change the overall rate of skin-related adverse events (AEs) compared to full doses.

However, patients with smaller body sizes experienced fewer skin-related AEs when on a reduced dose, and this dose reduction did not negatively impact their cancer-free survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of apalutamide dose reduction on skin-related adverse events in patients with advanced prostate cancer: A multicenter retrospective study. Oishi, T., Hatakeyama, S., Tabata, R., et al.[2023]

Apalutamide, an oral medication for non-metastatic castration-resistant prostate cancer, can cause a range of skin reactions, including a rare lichenoid reaction, as demonstrated in a case study of a patient after 4 months of treatment.

This case highlights the importance of a multidisciplinary approach in identifying and managing drug-related adverse events, which can improve diagnosis and treatment strategies for patients experiencing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide-induced lichenoid reaction in a patient with non-metastatic castrate-resistant prostate cancer. Cremante, M., Puglisi, S., Gandini, A., et al.[2023]

Apalutamide, an androgen receptor inhibitor for high-risk non-metastatic castration-resistant prostate cancer, shows rapid absorption and a large distribution volume, indicating effective body-wide delivery after oral administration.

In a study involving 1092 subjects, the pharmacokinetics of apalutamide and its metabolite were characterized, revealing low inter-individual variability and no significant predictors affecting drug clearance, suggesting consistent dosing effects across different patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Apalutamide and its Active Metabolite N-Desmethyl-Apalutamide in Healthy and Castration-Resistant Prostate Cancer Subjects. Pérez-Ruixo, C., Pérez-Blanco, JS., Chien, C., et al.[2021]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Efficacy and safety of apalutamide in Japanese patients with nonmetastatic castration-resistant prostate cancer: a subgroup analysis of a randomized, double-blind, placebo-controlled, Phase-3 study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide. [2022]

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

Apalutamide in the treatment of castrate-resistant prostate cancer: evidence from clinical trials. [2020]

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

Pharmacokinetics, Safety, and Antitumor Effect of Apalutamide with Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer: Phase Ib Study. [2021]

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

Apalutamide in combination with autophagy inhibitors improves treatment effects in prostate cancer cells. [2021]

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

Effects of apalutamide dose reduction on skin-related adverse events in patients with advanced prostate cancer: A multicenter retrospective study. [2023]

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

Apalutamide-induced lichenoid reaction in a patient with non-metastatic castrate-resistant prostate cancer. [2023]

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

Apalutamide for the Treatment of Nonmetastatic Castration-Resistant Prostate Cancer. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Apalutamide and its Active Metabolite N-Desmethyl-Apalutamide in Healthy and Castration-Resistant Prostate Cancer Subjects. [2021]

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

Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. [2022]