Apalutamide + Hormone Therapy for Prostate Cancer

Recruiting at 2 trial locations

Overseen By Karen Hoffman, MD

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Seizure threshold medications

Disqualifiers: Seizure history, Uncontrolled hypertension, Active infection, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well apalutamide, when used with hormone therapy, treats prostate cancer and reduces side effects like fatigue during radiation treatment. Participants will receive different combinations of hormone therapy (also known as androgen deprivation therapy or ADT), radiation, and apalutamide to identify the most effective approach. Men diagnosed with prostate cancer, who have had surgery, and plan to undergo additional treatments like radiation and hormone therapy may be suitable for this study. 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 that you stop taking medications known to lower the seizure threshold at least 4 weeks before starting the study treatment if you are in the group receiving apalutamide.

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

Research has shown that apalutamide is generally safe for use. In both real-world settings and clinical trials, it has proven effective and well-tolerated. Specifically, the ARON-3 study confirmed its efficacy and safety in everyday use and research settings.

The TITAN study demonstrated that combining apalutamide with androgen deprivation therapy (ADT) significantly reduced the risk of disease progression, indicating effective treatment with manageable side effects.

Patient feedback also provides valuable insights. In the SPARTAN and TITAN studies, only a small percentage of patients (0.2%) experienced serious side effects, such as blood flow issues in the brain, suggesting that serious side effects are rare.

Overall, evidence supports that apalutamide, whether used alone or with ADT, is generally safe for patients with prostate cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about apalutamide for prostate cancer because it offers a new approach by directly targeting androgen receptors, potentially reducing cancer cell growth more effectively than standard treatments. Unlike traditional androgen deprivation therapy (ADT) alone, apalutamide combined with radiation therapy might enhance treatment efficacy with fewer side effects. Additionally, using apalutamide for a shorter duration alongside radiation could offer a more convenient and less taxing option for patients, while still maintaining effectiveness.

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

Research shows that apalutamide, when combined with androgen deprivation therapy (ADT), extends the lives of prostate cancer patients. One study found that 65.1% of patients taking apalutamide with ADT were alive after 48 months, compared to 51.8% of those taking a placebo with ADT. Apalutamide also reduced the risk of death by 23% at 24 months compared to enzalutamide. Additionally, the combination of apalutamide and ADT decreased the risk of cancer progression by 52%. In this trial, participants will receive varying combinations of apalutamide, ADT, and radiation therapy. These findings suggest that apalutamide can effectively improve outcomes in prostate cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Karen E. Hoffman

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for men with detectable PSA levels after prostatectomy, indicating prostate cancer may still be present. Participants should be undergoing radiation therapy and hormone treatment for their condition.

Inclusion Criteria

I can understand English or Spanish.

I am over 18 years old.

My prostate cancer diagnosis was confirmed through a tissue examination.

Exclusion Criteria

I have used testosterone suppression therapy after prostate surgery.

I have a history of seizures or conditions that could lead to seizures.

I haven't had serious heart problems in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 6 months of apalutamide monotherapy or 6 months of GnRH-based ADT, with radiation therapy for prostate cancer

6 months

Extended Treatment

Participants in the higher risk cohort receive 24 months of GnRH-based ADT plus apalutamide monotherapy

24 months

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Androgen Deprivation Therapy
• Apalutamide

Trial Overview The study aims to personalize prostate cancer treatment by testing if apalutamide can reduce fatigue compared to standard therapy in patients receiving post-operative radiation and hormone therapy.

How Is the Trial Designed?

Group I: Arm 4 Experimental Treatment 2 Interventions

Participants will receive 6 months of ADT, apalutamide, and radiation therapy.

Group II: Arm 3 Experimental Treatment 1 Intervention

Participants will receive 24 months of standard-of-care androgen deprivation therapy (ADT) and radiation therapy.

Group III: Arm 2 Experimental Treatment 1 Intervention

Participants will receive 6 months of apalutamide and radiation therapy.

Group IV: Arm 1 Experimental Treatment 1 Intervention

Participants will receive 6 months of standard-of-care androgen deprivation therapy (ADT) and radiation therapy.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

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 involving 1,052 patients with metastatic castration-sensitive prostate cancer, apalutamide combined with androgen deprivation therapy (ADT) led to significant improvements in prostate-specific antigen (PSA) decline compared to placebo, with 90% of patients achieving a PSA decline of at least 50%.

The study found that achieving a deep PSA decline (≥90% or to ≤0.2 ng/ml) within 3 months of treatment with apalutamide was strongly associated with better overall survival and progression-free survival, indicating that rapid PSA response can be a predictor of long-term treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer. Chowdhury, S., Bjartell, A., Agarwal, N., et al.[2023]

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]

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, 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, when used in combination with androgen deprivation therapy (ADT), significantly improves overall survival in patients with advanced prostate cancer, as demonstrated in two phase 3 clinical trials (SPARTAN and TITAN).

The treatment is well tolerated across a diverse patient population, including those with varying risk levels of metastatic disease, and its side effects are manageable, not adversely affecting the patients' quality of life compared to ADT alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of apalutamide in the treatment landscape for patients with advanced prostate cancer: an expert opinion statement of European clinical practice. Bögemann, M., Facchini, G., Bauernhofer, T., 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]

Citations

1. 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.

2. jnj.com jnj.com/innovativemedicine/us/news-center/oncology/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 enzalutamide.

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/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.

5. 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 ...

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. 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 ...