Apalutamide + Hormone Therapy for Prostate Cancer

Not currently recruiting at 354 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Aragon Pharmaceuticals, Inc.

Must be taking: GnRH agonists

Must not be taking: Anti-androgens, Glucocorticoids

Disqualifiers: Metastasis, Seizure history, Others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 30 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of a new drug, apalutamide (also known as Erleada), with hormone therapy to determine if it helps men with high-risk prostate cancer live longer without the cancer spreading. The trial compares this drug combo to a placebo (a pill with no active medicine) to assess any real benefit. It targets men who plan to undergo radiation therapy for prostate cancer and have not received certain treatments or surgeries for it before. Participants should not have cancer that has spread to distant parts of the body. 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 protocol does not specify if you must stop taking your current medications, but certain medications are not allowed, such as systemic glucocorticoids, 5-alpha reductase inhibitors, and chronic opioid analgesics. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research has shown that apalutamide is generally well-tolerated by patients. In various studies, including the SPARTAN and TITAN trials, only a small number of patients (0.2%) experienced serious side effects, such as problems with blood flow in the brain, indicating that such events are rare.

Additionally, real-world data supports the safety of apalutamide for treating prostate cancer. While no treatment is without risk, available data demonstrates that apalutamide has a strong safety record. Participants in this current trial can expect a similar level of safety based on past studies and real-world experiences. ^{1 2 3 4 5}

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

Researchers are excited about apalutamide for prostate cancer because it offers a novel approach by specifically blocking the action of androgen receptors, which are crucial for prostate cancer growth. Unlike traditional hormone therapies that often involve direct hormone suppression, apalutamide targets the receptors themselves, potentially leading to more effective management of the disease. Additionally, when combined with GnRH agonists and radiation, apalutamide might enhance treatment outcomes by more comprehensively tackling cancer cell proliferation pathways. This combination could be especially beneficial for patients, potentially providing a more robust treatment option compared to current standard therapies.

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

Research has shown that apalutamide, one of the treatments in this trial, effectively treats prostate cancer when combined with hormone therapy. Studies indicate that combining apalutamide with androgen deprivation therapy (ADT) improves survival rates. Specifically, after 48 months, 65.1% of patients taking apalutamide with ADT were alive, compared to 51.8% of those taking a placebo with ADT. Additionally, apalutamide lowered the risk of death by 23% over 24 months in certain prostate cancer cases. These findings suggest that this treatment can improve outcomes for prostate cancer patients. Participants in this trial will receive either apalutamide or a placebo, alongside hormone therapy, to further evaluate its effectiveness. ^{2 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 over 18 with high-risk, localized or locally advanced prostate cancer who are set to receive primary radiation therapy. They must be in good health with a low Charlson index (<=3), able to swallow pills, and have normal liver function and adequate blood counts. Participants should not have had prior treatments for prostate cancer, no history of seizures or conditions that may cause them, and agree to use condoms.

Inclusion Criteria

Charlson index (CCI) <=3

Signed, written, informed consent

I am fully active or can carry out light work.

Exclusion Criteria

I have had both testicles surgically removed.

I have been treated with hormone therapy for prostate cancer for more than 3 months.

I have had treatment for prostate cancer, such as chemotherapy or surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive apalutamide or placebo plus GnRH agonist and radiation therapy

30 months

Regular visits for treatment administration and monitoring

Posttreatment

Participants are monitored for safety and effectiveness after treatment completion

4-8 weeks

Long-term Follow-up

Participants are monitored for metastasis-free survival and other outcomes

108 months

What Are the Treatments Tested in This Trial?

Interventions

• Apalutamide
• Apalutamide Placebo
• Bicalutamide
• Bicalutamide Placebo
• GnRH (agonist)
• Primary Radiation Therapy

Trial Overview The trial is testing if adding apalutamide plus GnRH agonist to the standard radiation treatment improves survival without metastasis in men with high-risk prostate cancer. It compares this combination against placebo versions while all participants receive radiation therapy.

How Is the Trial Designed?

Group I: Apalutamide Experimental Treatment 4 Interventions

Participants will receive apalutamide (240 mg), by mouth, once daily for overall 30 months, plus bicalutamide placebo, by mouth, once daily, for four months from randomization. All participants are treated with gonadotropin releasing hormone (GnRH) agonist for 30 months from randomization and radiation therapy to the prostate started at about 8 weeks after randomization.

Group II: Control group Active Control 4 Interventions

Participants will receive apalutamide placebo, by mouth, once daily for overall 30 months, plus bicalutamide (50 mg), by mouth, once daily, for four months from randomization. All participants are treated with gonadotropin releasing hormone (GnRH) agonist for 30 months from randomization and radiation therapy to the prostate started at about 8 weeks after randomization.

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]

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]

Apalutamide demonstrated stronger radio-sensitizing effects compared to bicalutamide in both hormone-sensitive and hormone-resistant prostate cancer cell lines, suggesting it may enhance the effectiveness of radiotherapy.

In vivo studies showed that combining apalutamide with radiotherapy resulted in significantly greater tumor necrosis in mouse models, indicating a potential for improved treatment outcomes in prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide radio-sensitisation of prostate cancer. Kakouratos, C., Kalamida, D., Lamprou, I., et al.[2023]

The SAVE trial is a Phase II study involving 202 men with advanced prostate cancer, comparing the effects of apalutamide combined with salvage radiotherapy against androgen-deprivation therapy plus salvage radiotherapy.

The primary goal is to evaluate sexual function after nine months of treatment, while also assessing quality of life, safety, and short-term efficacy of apalutamide, highlighting its potential benefits in managing prostate cancer post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II open-label study investigating apalutamide in patients with biochemical progression after radical prostatectomy. Dirix, P., Strijbos, M., den Mooter, TV., et al.[2021]

In a study of 318 prostate cancer patients with a median follow-up of 56 months, both radiotherapy combined with GnRHa and radiotherapy combined with bicalutamide showed similar five-year biochemical relapse-free survival rates (85.5% for GnRHa and 88.3% for bicalutamide).

Bicalutamide may be a suitable alternative for patients who prefer to avoid the side effects associated with GnRHa, highlighting the need for further randomized trials to compare these two treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy Plus GnRH Analogue Versus High Dose Bicalutamide: A Case Control Study. Buwenge, M., Deodato, F., Macchia, G., et al.[2020]

Apalutamide effectively blocks androgen receptor signaling in metastatic hormone-sensitive prostate cancer, leading to a rapid decrease in PSA levels and increased testosterone during monotherapy, indicating its efficacy in treatment.

Administering apalutamide 1 hour before GnRH agonists not only simplifies the treatment process but also effectively prevents testosterone flare-up, achieving castration levels of testosterone by day 28 without worsening side effects like dysuria or bone pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of PSA Flare With Apalutamide Administered 1 Hour in Advance With GnRH Agonists: Case Report. Hu, Z., Liu, Z., Chen, Z., 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]

Citations

1. 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 ...

2. erleadahcp.com erleadahcp.com/efficacy/

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.

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39893578/

Real-world clinical usage and efficacy of apalutamide in ... The secondary outcomes were the efficacy of apalutamide: PSA response (50% or 90% decline), progression-free survival, and skin-adverse events ( ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2588931124002530

Apalutamide in Metastatic Castration-sensitive Prostate ... Our results show that apalutamide is a safe and effective drug in the real-world setting as well as in clinical trials.

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

PATIENT-REPORTED OUTCOMES FOR HRQoL 1-6 Across the SPARTAN and TITAN studies, 3 patients (0.2%) treated with ERLEADA® and 2 patients (0.2%) treated with placebo died from a cerebrovascular event.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39613567/

Results from the Multicenter Real-world ARON-3 Study Our results show that apalutamide is a safe and effective drug in the real-world setting as well as in clinical trials.

8. 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 ...