Apalutamide for Prostate Cancer

Not currently recruiting at 7 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Antiandrogens, Estrogens, Antipsychotics, others

Disqualifiers: Metastases, Neuroendocrine differentiation, Seizure, others

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

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: 7

Duration: 3-4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a low dose of apalutamide (also known as Erleada) can reduce PSA levels, a marker linked to prostate cancer growth. Apalutamide blocks testosterone's effect, potentially managing prostate cancer before surgery. It may suit men with prostate cancer confined to the prostate gland who have not received prior hormonal treatments. The goal is to determine if this approach can delay the need for more aggressive treatments like surgery or radiation. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot have had prior hormonal treatments for prostate cancer. You also cannot use drugs that lower the seizure threshold or have category X interactions with apalutamide. If you're on stable doses of 5-alpha reductase inhibitors, you can continue as long as there's no dose change.

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

Research has shown that apalutamide is generally safe and well-tolerated. In various studies, including real-world settings and clinical trials, apalutamide proved effective with manageable side effects. One study found that only 0.2% of patients experienced a serious event like a stroke, related to blood vessels in the brain. This low percentage suggests that serious side effects are rare.

Patients using apalutamide have reported some side effects, but these are usually mild and similar to those seen with other treatments. Common side effects might include fatigue or a skin rash, but these are not usually severe.

In summary, apalutamide has a strong safety record based on current evidence. While any medication can have side effects, the risk of serious problems with apalutamide appears to be low. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for prostate cancer, which often include androgen deprivation therapy (ADT) and chemotherapy, apalutamide offers a unique approach by directly inhibiting the androgen receptor, a key driver of prostate cancer cell growth. Researchers are excited about apalutamide because it specifically targets the receptors, potentially reducing the cancer's ability to use androgens for growth. Additionally, apalutamide is taken orally, providing a more convenient administration compared to some injectable treatments. This targeted mechanism and ease of use make apalutamide a promising option for those with prostate cancer.

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

Research has shown that apalutamide, which participants in this trial will receive, can effectively block the effects of testosterone on prostate cancer cells, potentially slowing the cancer's growth. In studies with men whose prostate cancer has spread and still responds to hormone therapy, apalutamide reduced the risk of death by 23% over two years. After four years, more men taking apalutamide were alive compared to those taking a placebo. Many patients also experienced a significant drop in PSA levels, indicating reduced prostate cancer activity. These findings suggest that apalutamide could be a promising treatment for managing prostate cancer. ^{2 5 6 7 8}

Who Is on the Research Team?

Juan Chipollini

Principal Investigator

University of Arizona Cancer Center - Prevention Research Clinic

Are You a Good Fit for This Trial?

Men over 18 with prostate cancer confined to the gland, suitable for surgery, and a PSA level <=20 ng/ml. They must be in good physical condition (Karnofsky >=70%), have no severe heart issues or recent strokes, not taking certain drugs that interact with apalutamide or lower seizure threshold, and agree to use contraception.

Inclusion Criteria

Willing to use adequate contraception (barrier method; abstinence; subject has had a vasectomy; or partner is using effective birth control or is postmenopausal) for the duration of study participation

Current serum PSA =< 20 ng/ml

Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) < 2.5 x institutional ULN

Exclusion Criteria

My morning testosterone levels are below 200 ng/dL.

I have received or am receiving hormone therapy for prostate cancer.

I am not taking any medications that strongly interact with apalutamide.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low dose apalutamide orally for 3 to 4 weeks before prostate surgery

3-4 weeks

Regular blood sample collections throughout the study

Follow-up

Participants are monitored for safety and effectiveness after treatment, including post-operative assessments

3 months

Follow-up visits at 7-10 days, 60 days, and 3 months post-prostatectomy

What Are the Treatments Tested in This Trial?

Interventions

• Apalutamide

Trial Overview The trial is testing if low doses of Apalutamide can reduce PSA levels when given for 3-4 weeks before prostate removal surgery. It's a phase IIa study checking if this treatment could delay more aggressive therapy in men with localized prostate cancer.

How Is the Trial Designed?

Group I: Treatment (apalutamide) Experimental Treatment 3 Interventions

Patients receive apalutamide PO on study. Patients also undergo collection of blood samples throughout the study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

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, 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]

A total of 4,156 adverse event reports related to apalutamide were analyzed from the FDA's database, revealing 100 significant adverse events, with common issues including rash, fatigue, and diarrhea.

The most notable safety concern was related to skin disorders, highlighting the need for increased monitoring of dermatological side effects in patients treated with apalutamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world disproportionality analysis of apalutamide: data mining of the FDA adverse event reporting system. Fang, Z., Xu, Z., Zhu, W., et al.[2023]

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 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]

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]

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 ...