Apalutamide for Prostate Cancer

Recruiting at 6 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

34 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Apalutamide for prostate cancer?

Research shows that Apalutamide, when added to standard hormone therapy, significantly improves survival and delays disease progression in men with both metastatic and non-metastatic prostate cancer. It helps patients live longer without their cancer getting worse, while maintaining their quality of life. ^{1 2 3 4 5}

Is apalutamide safe for humans?

Apalutamide, also known as Erleada, is generally considered safe for humans, but it can cause side effects like skin rashes, fatigue, diarrhea, hot flashes, and high blood pressure. Some less common side effects include increased eosinophil count (a type of white blood cell), bacterial pneumonia, and skin reactions. ^{1 2 5 6 7}

What makes the drug Apalutamide unique for prostate cancer treatment?

Apalutamide is unique because it is an oral drug that specifically targets and blocks androgen receptors, which are involved in the growth of prostate cancer cells. It is used in combination with androgen deprivation therapy (ADT) to significantly improve survival and delay disease progression in both metastatic castration-sensitive and non-metastatic castration-resistant prostate cancer. ^{1 2 5 7 8}

What is the purpose of this trial?

Apalutamide is an anti-androgen that blocks the effect of testosterone on prostate cancer growth. This phase IIa trial is designed to determine whether very low doses of apalutamide, given for 3 to 4 weeks before prostate surgery to men with prostate cancer confined to the prostate gland, reduces plasma levels of PSA (a biomarker of apalutamide's ability to block testosterone). If low dose apalutamide lowers PSA levels in this setting, further study of this agent in men with localized prostate cancer who wish to delay definitive therapy with surgery or radiation may be warranted.

Research Team

Juan Chipollini

Principal Investigator

University of Arizona Cancer Center - Prevention Research Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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, 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]

References

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

Apalutamide: First Global Approval. [2019]

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

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

3. 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]

4. 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]

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

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

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

A real-world disproportionality analysis of apalutamide: data mining of the FDA adverse event reporting system. [2023]

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

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

8. 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]