Apalutamide for Castration-Resistant Prostate Cancer

(SPARTAN Trial)

Recruiting at 392 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Aragon Pharmaceuticals, Inc.

Must be taking: Androgen deprivation therapy

Must not be taking: Second-gen anti-androgens, CYP17 inhibitors

Disqualifiers: Metastases, Seizure history, Uncontrolled hypertension, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 43 months

1207 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires a 4-week period without certain medications like first-generation anti-androgens, 5-alpha reductase inhibitors, estrogens, and other anti-cancer therapies before starting. You should discuss your current medications with the trial team to see if any need to be stopped.

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

Research shows that Apalutamide, when used with androgen deprivation therapy (ADT), significantly improves survival and delays disease progression in patients with both metastatic and non-metastatic castration-resistant prostate cancer. It has been shown to prolong the time before the cancer spreads and maintain quality of life compared to a placebo. ^{1 2 3 4 5}

Is apalutamide safe for humans?

Apalutamide, also known as Erleada, is generally well tolerated in patients with prostate cancer, with fatigue being the most common side effect. It has been studied in various clinical trials and has not shown substantial safety differences compared to placebo. ^{1 4 5 6 7}

What makes the drug Apalutamide unique for treating castration-resistant prostate cancer?

Apalutamide is unique because it is an oral drug that directly blocks the androgen receptor, which is crucial in prostate cancer growth, and it is specifically approved for both non-metastatic and metastatic forms of castration-resistant prostate cancer. It has been shown to significantly improve survival and delay disease progression when added to standard hormone therapy, while maintaining quality of life. ^{1 2 3 4 5}

Research Team

Aragon Pharmaceuticals, Inc. Clinical Trial

Principal Investigator

Aragon Pharmaceuticals, Inc.

Eligibility Criteria

Men with non-metastatic castration-resistant prostate cancer, showing a high risk of developing metastases and having a PSA doubling time of 10 months or less. Participants must be on continuous ADT with rising PSA levels, maintain low testosterone, and have no prior treatments that disqualify them such as second-generation anti-androgens or chemotherapy for prostate cancer.

Inclusion Criteria

I've stopped my first anti-androgen treatment for 4 weeks and my cancer is still getting worse.

My prostate cancer is growing despite hormone therapy, with increasing PSA levels.

I have been on a stable dose of medication for bone loss for at least 4 weeks.

Exclusion Criteria

History or evidence of any of the following conditions: any prior malignancy within 5 years prior to randomization (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission); severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events, or clinically significant ventricular arrhythmias within 6 months prior to randomization; uncontrolled hypertension; gastrointestinal disorder affecting absorption; active infection; and any other condition that, in the opinion of the investigator, would impair the patient's ability to comply with study procedures

My cancer symptoms need medical treatment.

I have not had treatments like radiopharmaceuticals for my prostate cancer before it spread.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the investigational medication or placebo daily in cycles of 4 weeks

Up to approximately 43 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Apalutamide
• Placebo

Trial Overview The trial is testing the effectiveness and safety of Apalutamide compared to a placebo in men with high-risk non-metastatic castration-resistant prostate cancer. The goal is to see if Apalutamide can prevent the cancer from spreading.

Participant Groups

Group I: Treatment Arm A: Apalutamide Experimental Treatment 1 Intervention

Group II: Treatment Arm B: Placebo Placebo Group 1 Intervention

Apalutamide is already approved in United States, European Union for the following indications:

Approved in United States as Erleada for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic castration-sensitive prostate cancer (mCSPC)

Approved in European Union as Erleada for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic castration-sensitive prostate cancer (mCSPC)

Who Is Running the Clinical Trial?

Aragon Pharmaceuticals, Inc.

Lead Sponsor

Trials

17

Recruited

5,400+

Findings from Research

In a phase III study (TITAN) involving men with metastatic castration-sensitive prostate cancer, adding apalutamide to androgen deprivation therapy significantly improved median radiographic progression-free survival and overall survival.

Apalutamide was found to maintain health-related quality of life and had a safety profile similar to that of placebo when combined with androgen deprivation therapy, expanding treatment options for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. Hoy, SM.[2021]

In the SPARTAN study involving 1207 patients with nonmetastatic castration-resistant prostate cancer, apalutamide significantly improved health-related quality of life (HRQoL) compared to placebo, with patients maintaining better scores over time.

Patients receiving apalutamide experienced minimal side effects and reported no worsening of fatigue, while those on placebo showed a decline in quality of life after about one year, highlighting the efficacy and tolerability of apalutamide in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. Oudard, S., Hadaschik, B., Saad, F., 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 the SPARTAN trial, apalutamide significantly improved metastasis-free survival in men with non-metastatic castration-resistant prostate cancer (nmCRPC) receiving androgen-deprivation therapy, demonstrating its efficacy as a treatment option.

Apalutamide was generally well tolerated, with fatigue being the most common side effect, indicating a favorable safety profile while maintaining health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. Al-Salama, ZT.[2020]

Apalutamide is an oral androgen receptor inhibitor that effectively blocks androgen effects, and it received its first global approval in February 2018 for treating non-metastatic castration-resistant prostate cancer (nmCRPC).

Currently, apalutamide is being tested in phase III trials for various prostate cancer stages, including metastatic castration-resistant prostate cancer and high-risk localized prostate cancer, indicating its potential for broader applications in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: First Global Approval. Al-Salama, ZT.[2019]

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]

This clinical trial aims to evaluate the efficacy and safety of apalutamide in 110 patients with metastatic castration-resistant prostate cancer, focusing on the primary outcome of prostate-specific antigen (PSA) response rate, defined as a ≥50% decline from baseline at 12 weeks.

The study will also assess various secondary outcomes, including time to PSA progression and overall survival, while monitoring for any grade 3 or 4 adverse events, ensuring a comprehensive evaluation of both effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of apalutamide in patients with metastatic castration-resistant prostate cancer (GENESIS): protocol for a multicentre, open-label, single-arm clinical trial. Miyake, H., Kakei, Y., Nakano, Y., et al.[2023]

References

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

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. [2022]

3. 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]

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

Apalutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. [2020]

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

Apalutamide: First Global Approval. [2019]

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

Efficacy and safety of apalutamide in patients with metastatic castration-resistant prostate cancer (GENESIS): protocol for a multicentre, open-label, single-arm clinical trial. [2023]