Apalutamide for Prostate Cancer

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ARN-509 (also known as apalutamide, a type of hormone therapy) for men with advanced prostate cancer that doesn't respond to standard hormone therapy. The goal is to find a safe dose and evaluate its effectiveness for different types of prostate cancer, such as non-metastatic cases with rapidly rising PSA levels or metastatic cancer. Participants may qualify if they have prostate cancer unresponsive to hormone therapy, have not tried certain other medications, and do not have brain metastases or severe health issues. As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial group, offering participants a chance to contribute to groundbreaking advancements in prostate cancer treatment.

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.

Is there any evidence suggesting that ARN-509 is likely to be safe for humans?

Research has shown that apalutamide (ARN-509) is generally safe and well-tolerated for people with prostate cancer. In one study, 80% of patients who had not previously taken abiraterone continued using apalutamide without major problems. Even among those who had used abiraterone before, 43% were able to stay on apalutamide. This suggests that many patients can handle the drug well.

Another study examined men with high-risk prostate cancer that had not spread and also found apalutamide to be safe. Most side effects were manageable, meaning they were not too severe and could be treated or adjusted.

These findings indicate that apalutamide is generally safe for those considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about ARN-509 for prostate cancer because it targets the androgen receptor pathway more effectively than many current treatments. Unlike traditional options such as hormone therapies that indirectly lower androgen levels, ARN-509 directly blocks the androgen receptor, potentially offering stronger and more direct inhibition of cancer growth. This direct targeting could lead to improved outcomes for patients, especially those with castration-resistant prostate cancer (CRPC), by slowing disease progression and enhancing quality of life.

What evidence suggests that ARN-509 might be an effective treatment for advanced castration-resistant prostate cancer?

Research shows that Apalutamide, also known as ARN-509, may help treat castration-resistant prostate cancer (CRPC). In this trial, participants with non-metastatic CRPC will receive Apalutamide. Studies have found that it can significantly extend the time patients live without cancer spreading and reduce the risk of death by 25% compared to a placebo. For those with metastatic CRPC, Apalutamide will be given to treatment-naive participants, with studies showing that 80% of these patients continue treatment. Additionally, participants with metastatic CRPC who have previously used abiraterone will also receive Apalutamide, which has shown it can help slow cancer growth. Overall, these findings suggest that Apalutamide could be a good option for different stages of CRPC. ^{1 5 6 7 8}

Who Is on the Research Team?

Aragon Pharmaceuticals, Inc Clinical Trial

Principal Investigator

Aragon Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

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

I have been treated with ketoconazole before.

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

I have been treated with abiraterone before.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5543693/

Safety and Antitumor Activity of Apalutamide (ARN-509) in ... Apalutamide was safe, well tolerated, and demonstrated clinical activity in mCRPC with 80% of AAP-naïve and 43% of post-AAP patients remaining on treatment for ...

2. bmjopen.bmj.com bmjopen.bmj.com/content/13/3/e070173

Efficacy and safety of apalutamide in patients with ... This trial is a prospective, multicentre, investigator-initiated study assessing apalutamide in patients with metastatic castration-resistant prostate cancer.

3. esmoopen.com esmoopen.com/article/S2059-7029(20)30178-2/fulltext

The earlier the better? Apalutamide for non-metastatic ... Overall, apalutamide was well tolerated. The most reported side effects were fatigue, skin rash, weight decrease, arthralgia, fractures and falls. The full ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0302283816301336

Phase 2 Study of the Safety and Antitumor Activity ... In high-risk nmCRPC patients, apalutamide was safe with robust activity based on durable PSA responses and disease control.

5. onclive.com onclive.com/view/apalutamide-improves-survival-in-metastatic-castration-sensitive-prostate-cancer

Apalutamide Improves Survival in Metastatic Castration ... The approval was based on data from the phase III SPARTAN trial, in which apalutamide led to a 72% reduction in the risk of metastasis or death in patients with ...

6. aacrjournals.org aacrjournals.org/clincancerres/article/23/14/3544/122974/Safety-and-Antitumor-Activity-of-Apalutamide-ARN

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 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01946204

NCT01946204 | A Study of Apalutamide (ARN-509) in Men ... The purpose of this study is to evaluate the efficacy and safety of apalutamide in adult men with high-risk non-metastatic castration-resistant prostate cancer.

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1903307

Apalutamide for Metastatic, Castration-Sensitive Prostate ... In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) ...