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

26 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies how well apalutamide, with or without precise radiation therapy (SBRT), works in treating prostate cancer that resists typical hormone treatments. Apalutamide blocks testosterone, which helps slow cancer growth. SBRT uses focused radiation to kill cancer cells while sparing healthy tissue. The goal is to see if combining these treatments is more effective than using apalutamide alone. Apalutamide is a newer anti-androgen drug that has shown promise in improving the effectiveness of radiotherapy in prostate cancer treatment.

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.

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

Research shows that Apalutamide, when combined with androgen deprivation therapy, significantly improves survival and delays disease progression in patients with advanced prostate cancer, as seen in the TITAN and SPARTAN studies. ^{1 2 3 4 5}

Is the combination of Apalutamide and radiation therapy safe for humans?

Apalutamide, used for prostate cancer, is generally well tolerated with fatigue being the most common side effect. It has been studied in combination with radiation therapy, showing a safety profile similar to other treatments, without major differences in adverse effects. ^{2 3 6 7 8}

What makes the drug Apalutamide unique for prostate cancer treatment?

Apalutamide is unique because it is an oral drug that directly inhibits the androgen receptor, which is crucial in prostate cancer growth, and it is used in combination with stereotactic body radiation therapy (SBRT) to potentially enhance treatment effectiveness. This combination aims to improve outcomes for patients with prostate cancer by targeting the cancer cells more precisely and effectively than traditional treatments. ^{2 3 4 6 9}

Research Team

Rahul Aggarwal, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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 Business School

John (Jack) Lawrence

Janssen Pharmaceuticals

Chief Medical Officer since 2023

MD from University of Virginia School of Medicine

Findings from Research

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]

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 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, 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 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 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 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. 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]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Phase II open-label study investigating apalutamide in patients with biochemical progression after radical prostatectomy. [2021]

4. Netherlands 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. [2022]

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

Apalutamide: First Global Approval. [2019]

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

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

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]

9. 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]