Apalutamide + Hormone Therapy for Prostate Cancer

Recruiting at 284 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Aragon Pharmaceuticals, Inc.

Must be taking: GnRH agonists

Must not be taking: Anti-androgens, Glucocorticoids

Disqualifiers: Metastasis, Seizure history, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 30 months

1503 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests whether combining apalutamide with another treatment helps men with high-risk prostate cancer undergoing radiation therapy. The treatment aims to block and reduce male hormones that fuel cancer growth, potentially preventing the cancer from spreading. Apalutamide has been developed for treating prostate cancer and has shown effectiveness.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but certain medications are not allowed, such as systemic glucocorticoids, 5-alpha reductase inhibitors, and chronic opioid analgesics. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research shows that Apalutamide, when added to hormone therapy, significantly improves survival and delays disease progression in men with prostate cancer, while maintaining quality of life. It has been effective in both metastatic and non-metastatic prostate cancer, making it a promising option for patients. ^{1 2 3 4 5}

Is Apalutamide safe for humans?

Apalutamide is generally considered safe and well-tolerated for treating prostate cancer, with fatigue being the most common side effect reported. It has been approved in the USA and EU for specific types of prostate cancer, and studies have shown it maintains quality of life while providing treatment benefits. ^{1 3 5 6 7}

How is the drug Apalutamide with hormone therapy unique for prostate cancer treatment?

Apalutamide is a next-generation oral drug that blocks the effects of male hormones (androgens) by directly binding to their receptor, and when combined with hormone therapy and radiation, it offers a novel approach for treating prostate cancer by potentially improving survival and delaying the need for chemotherapy. ^{1 3 4 8 9}

Research Team

Aragon Pharmaceuticals, Inc. Clinical Trial

Principal Investigator

Aragon Pharmaceuticals, Inc.

Eligibility Criteria

Men over 18 with high-risk, localized or locally advanced prostate cancer who are set to receive primary radiation therapy. They must be in good health with a low Charlson index (<=3), able to swallow pills, and have normal liver function and adequate blood counts. Participants should not have had prior treatments for prostate cancer, no history of seizures or conditions that may cause them, and agree to use condoms.

Inclusion Criteria

Charlson index (CCI) <=3

Signed, written, informed consent

I am fully active or can carry out light work.

Exclusion Criteria

I have had both testicles surgically removed.

I have been treated with hormone therapy for prostate cancer for more than 3 months.

I have had treatment for prostate cancer, such as chemotherapy or surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive apalutamide or placebo plus GnRH agonist and radiation therapy

30 months

Regular visits for treatment administration and monitoring

Posttreatment

Participants are monitored for safety and effectiveness after treatment completion

4-8 weeks

Long-term Follow-up

Participants are monitored for metastasis-free survival and other outcomes

108 months

Treatment Details

Interventions

• Apalutamide
• Apalutamide Placebo
• Bicalutamide
• Bicalutamide Placebo
• GnRH (agonist)
• Primary Radiation Therapy

Trial Overview The trial is testing if adding apalutamide plus GnRH agonist to the standard radiation treatment improves survival without metastasis in men with high-risk prostate cancer. It compares this combination against placebo versions while all participants receive radiation therapy.

Participant Groups

Group I: Apalutamide Experimental Treatment 4 Interventions

Participants will receive apalutamide (240 mg), by mouth, once daily for overall 30 months, plus bicalutamide placebo, by mouth, once daily, for four months from randomization. All participants are treated with gonadotropin releasing hormone (GnRH) agonist for 30 months from randomization and radiation therapy to the prostate started at about 8 weeks after randomization.

Group II: Control group Active Control 4 Interventions

Participants will receive apalutamide placebo, by mouth, once daily for overall 30 months, plus bicalutamide (50 mg), by mouth, once daily, for four months from randomization. All participants are treated with gonadotropin releasing hormone (GnRH) agonist for 30 months from randomization and radiation therapy to the prostate started at about 8 weeks after randomization.

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?

Aragon Pharmaceuticals, Inc.

Lead Sponsor

Trials

17

Recruited

5,400+

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 effectively blocks androgen receptor signaling in metastatic hormone-sensitive prostate cancer, leading to a rapid decrease in PSA levels and increased testosterone during monotherapy, indicating its efficacy in treatment.

Administering apalutamide 1 hour before GnRH agonists not only simplifies the treatment process but also effectively prevents testosterone flare-up, achieving castration levels of testosterone by day 28 without worsening side effects like dysuria or bone pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of PSA Flare With Apalutamide Administered 1 Hour in Advance With GnRH Agonists: Case Report. Hu, Z., Liu, Z., Chen, Z., 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]

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]

Apalutamide demonstrated stronger radio-sensitizing effects compared to bicalutamide in both hormone-sensitive and hormone-resistant prostate cancer cell lines, suggesting it may enhance the effectiveness of radiotherapy.

In vivo studies showed that combining apalutamide with radiotherapy resulted in significantly greater tumor necrosis in mouse models, indicating a potential for improved treatment outcomes in prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide radio-sensitisation of prostate cancer. Kakouratos, C., Kalamida, D., Lamprou, I., et al.[2023]

In a study of 318 prostate cancer patients with a median follow-up of 56 months, both radiotherapy combined with GnRHa and radiotherapy combined with bicalutamide showed similar five-year biochemical relapse-free survival rates (85.5% for GnRHa and 88.3% for bicalutamide).

Bicalutamide may be a suitable alternative for patients who prefer to avoid the side effects associated with GnRHa, highlighting the need for further randomized trials to compare these two treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy Plus GnRH Analogue Versus High Dose Bicalutamide: A Case Control Study. Buwenge, M., Deodato, F., Macchia, G., et al.[2020]

References

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

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

Absence of PSA Flare With Apalutamide Administered 1 Hour in Advance With GnRH Agonists: Case Report. [2022]

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

Apalutamide: First Global Approval. [2019]

4. England pubmed.ncbi.nlm.nih.gov

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

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

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

6. 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]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Prospects of Treating Prostate Cancer through Apalutamide: A Mini-Review. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Apalutamide radio-sensitisation of prostate cancer. [2023]

9. Greece pubmed.ncbi.nlm.nih.gov

Radiotherapy Plus GnRH Analogue Versus High Dose Bicalutamide: A Case Control Study. [2020]