Apalutamide + Hormone Therapy for Prostate Cancer

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

Trial Summary

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.

What data supports the effectiveness of the drug apalutamide when used with hormone therapy for prostate cancer?

Research shows that adding apalutamide to hormone therapy significantly improves survival and delays disease progression in men with certain types of prostate cancer, such as metastatic castration-sensitive and non-metastatic castration-resistant prostate cancer. ^{1 2 3 4 5}

Is Apalutamide with Hormone Therapy safe for humans?

Apalutamide, when used with hormone therapy for prostate cancer, is generally well tolerated, but common side effects include skin reactions and fatigue. It has been studied in various types of prostate cancer, and while it improves survival and quality of life, patients should be aware of these potential side effects. ^{1 2 3 6 7}

How is the drug Apalutamide unique in treating 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 used in combination with hormone therapy to improve survival in both metastatic castration-sensitive and non-metastatic castration-resistant prostate cancer. ^{1 2 3 5 8}

What is the purpose of this trial?

1. Personalize treatment for prostate cancer based on how aggressive the disease is and 2. Learn if apalutamide-based treatment can help to reduce fatigue and other side effects of treatment in participants who are being treated with radiation therapy for prostate cancer, as compared to standard therapy.

Research Team

Karen E. Hoffman

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

MD

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]

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]

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]

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]

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]

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]

References

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

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

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

Apalutamide: First Global Approval. [2019]

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

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

4. England 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. [2023]

5. Ireland 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. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Apalutamide and its Active Metabolite N-Desmethyl-Apalutamide in Healthy and Castration-Resistant Prostate Cancer Subjects. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Apalutamide-induced lichenoid reaction in a patient with non-metastatic castrate-resistant prostate cancer. [2023]

8. 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]