Apalutamide for Castration-Resistant Prostate Cancer

(SPARTAN Trial)

Not currently recruiting at 451 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a drug called apalutamide for men with a specific type of prostate cancer that has not spread. The trial includes two groups: one receiving apalutamide and the other a placebo (a look-alike pill with no active drug). Men with a history of treatment-resistant prostate cancer, indicated by rising PSA levels despite hormone therapy, might be suitable candidates. Participants should not have cancer that has spread to distant organs or certain other medical conditions. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that apalutamide is likely to be safe for humans?

Research has shown that apalutamide is generally safe for people with prostate cancer. One study found that 67.7% of patients experienced some side effects, but most were mild. Only 6.5% faced more serious effects. Another study revealed that many patients with advanced prostate cancer could continue using the treatment for an extended period, indicating it is manageable for most. This suggests that apalutamide is safe for many, although some might experience mild to moderate side effects. ^{1 2 3 4 5}

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

Apalutamide is unique because it directly targets the androgen receptor, which plays a crucial role in the progression of castration-resistant prostate cancer. Unlike traditional hormone therapies that reduce androgen production, Apalutamide works by blocking the receptor itself, preventing cancer cells from using these hormones to grow. Researchers are excited about this treatment due to its potential to improve survival rates and delay disease progression more effectively than current options like enzalutamide and abiraterone. This targeted approach could offer patients a more effective and potentially less toxic option in their fight against prostate cancer.

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

In this trial, participants will receive either apalutamide or a placebo. Research has shown that apalutamide effectively treats a type of prostate cancer that hasn't spread and doesn't respond to lowering testosterone levels. Studies indicate that, when combined with hormone therapy, apalutamide delays cancer progression and extends patient survival. Real-world data also shows that starting treatment with apalutamide can reduce the risk of death in similar cases. Overall, evidence suggests that apalutamide can be a beneficial treatment option for this type of prostate cancer. ^{3 4 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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11384626/

Apalutamide for non-metastatic castration-resistant prostate ... Apalutamide plus androgen-deprivation therapy (ADT) improved outcomes in patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

2. jnj.com jnj.com/media-center/press-releases/erleada-apalutamide-demonstrates-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-compared-to-enzalutamide-in-patients-with-metastatic-castration-sensitive-prostate-cancer

ERLEADA® (apalutamide) demonstrates statistically ... Largest head-to-head real-world study in mCSPC demonstrated that ERLEADA® reduced risk of death by 23 percent at 24 months compared to ...

3. nature.com nature.com/articles/s41391-024-00929-6

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– ...

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

Apalutamide for Metastatic, Castration-Sensitive Prostate ... In our trial, initial therapy with apalutamide in patients with metastatic, castration-sensitive prostate cancer led to improved clinical outcomes. The intent ...

5. jheor.org jheor.org/article/121233-real-world-clinical-outcomes-and-treatment-patterns-among-black-and-non-black-patients-with-prostate-cancer-initiated-on-apalutamide-in-a-urology-sett

Real-World Clinical Outcomes and Treatment Patterns ... Apalutamide demonstrated robust real-world effectiveness with respect to progression to castration resistance, CRFS, and MFS, overall and among Black and non- ...

6. 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 ...

7. erleadahcp.com erleadahcp.com/patient-reported-outcomes/

PATIENT-REPORTED OUTCOMES FOR HRQoL 1-6 See patient-reported outcome data from pre-specified exploratory analysis, including HRQoL and more. See Full Safety & Prescribing Information.

8. link.springer.com link.springer.com/article/10.1007/s00432-024-05928-7

Apalutamide for non-metastatic castration-resistant ... Apalutamide was well tolerated in real world patients: adverse events occurred in 67.7% but were in the majority mild (≥ grade 3: 6.5%). Dose ...