Apalutamide + SBRT for Prostate Cancer

(PILLAR Trial)

Overseen By UCSF Genitourinary Cancer Clinical Trials Recruitment

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must be taking: LHRH analogues

Must not be taking: Seizure threshold medications

Disqualifiers: Visceral lesions, Seizure history, 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: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether apalutamide, with or without Stereotactic Body Radiation Therapy (SBRT), helps combat castration-resistant prostate cancer. Apalutamide stops testosterone from aiding cancer growth, while the radiation targets and kills cancer cells with minimal damage to normal tissue. Individuals with prostate cancer that progresses despite hormone therapy and who have not received certain other treatments might qualify for this trial. 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 requires stopping certain medications before participating. If you are taking first-generation anti-androgens, you need a 6-week period without them before starting the trial. Other medications, like those that lower the seizure threshold or certain herbal products, must be stopped at least 1 to 4 weeks before joining the trial.

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

Research has shown that apalutamide is generally safe for people with prostate cancer. One study found that only 0.2% of patients experienced serious issues, such as problems with blood flow in the brain. In real-world use and other studies, apalutamide has proven effective and well-tolerated.

Stereotactic body radiation therapy (SBRT) is also considered safe. Studies have demonstrated a low risk of side effects for men with prostate cancer. Many patients achieve good results with this precise type of radiation treatment. Overall, both treatments have maintained a good safety record, with few severe side effects reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike traditional prostate cancer treatments that often involve surgery or hormone therapy alone, apalutamide combined with stereotactic body radiation therapy (SBRT) offers a novel approach. Apalutamide is an oral medication that works by blocking the androgen receptor, a key driver of prostate cancer growth. This combination is unique because it pairs a systemic treatment with precise, high-dose radiation, potentially enhancing the effectiveness of both. Researchers are excited about this because it could lead to better control of the cancer with fewer side effects, offering a promising alternative for patients.

What evidence suggests that apalutamide and SBRT could be effective for prostate cancer?

Research has shown that apalutamide effectively treats prostate cancer, significantly improving survival rates. Specifically, after 48 months, 65.1% of patients taking apalutamide were still alive, compared to 51.8% of those on a placebo.

Stereotactic body radiation therapy (SBRT) is also a safe and effective treatment for prostate cancer. It uses precise radiation to target tumors, protecting healthy tissue. This trial will evaluate one arm with the combination of apalutamide and SBRT, while another arm will assess SBRT alone. Both treatments have shown promise individually, and ongoing research is examining their combined effectiveness. ^{2 5 6 7 8}

Who Is on the Research Team?

Rahul Aggarwal, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer that's resistant to hormone therapy and hasn't spread beyond five areas, as seen on a PSMA-PET scan. They must have low testosterone despite ongoing treatment, no recent seizures or heart issues, and not be taking certain medications. Participants need normal organ function tests and can't have started other treatments for this stage of cancer.

Inclusion Criteria

Signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial prior to randomization

Absolute neutrophil count (ANC) ≥ 1500/microliter

Platelets ≥ 75,000/microliter without transfusion and/or growth factors in the 3 months prior to randomization

Exclusion Criteria

I have or am at risk of having spinal cord compression.

I have stopped taking certain medications and treatments that could affect the trial results.

I haven't had serious heart issues or blood clots 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 apalutamide orally once daily for up to 52 weeks. In Arm I, participants also undergo stereotactic body radiation therapy for 1-5 fractions starting 60 days after the first dose of apalutamide.

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with a focus on PSA levels and adverse events.

30 days

Long-term Follow-up

Participants are monitored for treatment-related adverse events and PSA progression.

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Apalutamide
• Stereotactic Body Radiation Therapy

Trial Overview The trial is testing the effectiveness of apalutamide, a drug blocking testosterone use by tumor cells, with or without stereotactic body radiation therapy (SBRT), which precisely targets tumors in fewer high-dose treatments causing less damage to healthy tissue.

How Is the Trial Designed?

Group I: Arm I (apalutamide, SBRT) Experimental Treatment 2 Interventions

Participants receive apalutamide PO QD on days 1-28. Courses repeat every 28 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Beginning 60 days after first dose of apalutamide, participants also undergo stereotactic body radiation therapy for 1-5 fractions.

Group II: Arm II (SBRT) Active Control 1 Intervention

Participants receive apalutamide PO QD on days 1-28. Courses repeat every 28 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity.

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?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Janssen Pharmaceuticals

Industry Sponsor

Trials

87

Recruited

208,000+

Joaquin Duato

Janssen Pharmaceuticals

Chief Executive Officer since 2022

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

Dr. Jijo James, MD

Janssen Pharmaceuticals

Chief Medical Officer since 2014

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

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, 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 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 study involving 1207 patients with nonmetastatic castration-resistant prostate cancer, apalutamide significantly improved health-related quality of life (HRQoL) compared to placebo, with patients maintaining better scores over time.

Patients receiving apalutamide experienced minimal side effects and reported no worsening of fatigue, while those on placebo showed a decline in quality of life after about one year, highlighting the efficacy and tolerability of apalutamide in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. Oudard, S., Hadaschik, B., Saad, F., et al.[2022]

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]

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 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 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]

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]

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 ...