Apalutamide + ADT for Prostate Cancer

(PROTEUS Trial)

Recruiting at 266 trial locations

Overseen By Study Contact

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must be taking: Androgen deprivation therapy

Must not be taking: Androgen receptor antagonists, GnRHa

Disqualifiers: Distant metastasis, Prior prostate therapy, Heart disease, 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: 12 cycles of 28 days each

2517 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if using apalutamide and hormone therapy around the time of surgery can help men with high-risk prostate cancer by reducing the hormones that help the cancer grow.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have been treated with certain prostate cancer therapies or investigational agents recently, you may not be eligible to participate.

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

Research shows that adding Apalutamide to androgen deprivation therapy (ADT) significantly improves survival and delays disease progression in men with metastatic castration-sensitive prostate cancer. Studies like the TITAN trial have demonstrated that this combination extends overall survival and maintains quality of life compared to ADT alone. ^{1 2 3 4 5}

Is the combination of Apalutamide and ADT safe for humans?

The combination of Apalutamide (Erleada) and androgen deprivation therapy (ADT) has been studied in clinical trials and is generally considered safe, with safety profiles similar to placebo plus ADT. However, ADT can lead to increased body fat and decreased muscle mass, which are known side effects. ^{1 2 6 7 8}

What makes the drug Apalutamide + ADT unique for prostate cancer?

Apalutamide combined with androgen deprivation therapy (ADT) is unique because it is an oral drug that directly inhibits the androgen receptor, significantly improving survival outcomes in patients with both metastatic castration-sensitive and non-metastatic castration-resistant prostate cancer, while maintaining quality of life. ^{1 2 9 10 11}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

Men with high-risk, localized or locally advanced prostate cancer who are candidates for surgery to remove the prostate and pelvic lymph nodes. They must be willing to undergo 13 months of treatment, have a Gleason Score of at least 7, no distant metastasis (M0 stage), and not have had prior treatments for prostate cancer or certain cardiovascular events in the past year.

Inclusion Criteria

My prostate cancer is confirmed by tissue analysis.

I am fully active or have some restrictions but can still care for myself.

Contraceptive use by male participants (and female partners of male participants enrolled in the study who are of childbearing potential or are pregnant) should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies

Exclusion Criteria

I have been treated with hormone therapies for my cancer.

I haven't had serious heart issues or blood clots in the last year.

My cancer has not spread to distant parts of my body according to scans.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive six cycles of apalutamide or placebo plus androgen deprivation therapy (ADT), followed by radical prostatectomy with pelvic lymph node dissection, and an additional six cycles of treatment

12 cycles of 28 days each

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of metastasis-free survival and other outcomes

Up to 7 years and 5 months

Treatment Details

Interventions

• Androgen Deprivation Therapy (ADT)
• Apalutamide
• Placebo

Trial Overview The trial is testing if adding apalutamide to standard hormone therapy before and after surgical removal of the prostate improves outcomes like complete response rate and survival without metastasis compared to placebo plus hormone therapy.

Participant Groups

Group I: Placebo + ADT Experimental Treatment 2 Interventions

Participants will receive ADT with oral administration of matching placebo treatment daily in each cycle (each cycle of 28 days). Participants will receive six cycles of placebo treatment, followed by RP with pLND, followed by an additional six cycles of placebo treatment.

Group II: Apalutamide + ADT Experimental Treatment 2 Interventions

Participants will receive androgen deprivation therapy (ADT) plus oral administration of apalutamide 240 milligram (mg) (4 tablets of 60 mg each) daily in each cycle (each cycle of 28 days). Participants will receive six cycles of treatment, followed by radical prostatectomy (RP) with pelvic lymph node dissection (pLND), followed by an additional six cycles of treatment.

Androgen Deprivation Therapy (ADT) is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Non-metastatic high-risk prostate cancer

Approved in United States as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Non-metastatic high-risk prostate cancer

Approved in Canada as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Non-metastatic high-risk prostate cancer

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

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, 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 55 Japanese patients with nonmetastatic castration-resistant prostate cancer, apalutamide combined with ongoing androgen deprivation therapy significantly improved metastasis-free survival compared to placebo, with median MFS not reached in the apalutamide group versus 18.23 months in the placebo group.

The safety profile of apalutamide was similar to that observed in the global population, with no new safety concerns identified, indicating that it is a safe and effective treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of apalutamide in Japanese patients with nonmetastatic castration-resistant prostate cancer: a subgroup analysis of a randomized, double-blind, placebo-controlled, Phase-3 study. Uemura, H., Satoh, T., Tsumura, H., et al.[2022]

Apalutamide combined with androgen-deprivation therapy (ADT) significantly improved overall survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant prostate cancer (nmCRPC) across all age groups, demonstrating its efficacy regardless of age.

The treatment was well-tolerated and maintained health-related quality of life (HRQoL), although there was a potential trend of increasing adverse events with age, indicating that apalutamide is a safe option for older patients as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide efficacy, safety and wellbeing in older patients with advanced prostate cancer from Phase 3 randomised clinical studies TITAN and SPARTAN. Shen, J., Chowdhury, S., Agarwal, N., 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]

A study of 229 men with prostate cancer showed that androgen deprivation therapy (ADT) leads to significant muscle mass loss, particularly with newer agents abiraterone acetate (ABI) and enzalutamide (ENZA), which resulted in a median muscle volume loss of -4.8% and -5.5% at 6 months, respectively.

ADT regimens also have different effects on body fat composition: while ABI increased visceral adipose tissue (VAT) at 6 months, ENZA decreased it, indicating that these treatments affect fat distribution differently and highlight the distinct roles of androgens in body composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profiling of Skeletal Muscle and Adipose Tissue Depots in Men with Advanced Prostate Cancer Receiving Different Forms of Androgen Deprivation Therapy. Blow, TA., Murthy, A., Grover, R., et al.[2023]

In a study of 425 elderly patients receiving androgen deprivation therapy (ADT) for advanced prostate cancer, 15.5% of prescriptions did not align with European Association of Urology guidelines, potentially exposing patients to unnecessary side effects.

Despite some inappropriate prescriptions, patient compliance with ADT was high at 87.5%, and while 39% experienced complications, the predominant use of GnRH agonists suggests a common treatment approach among this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Appropriateness and complications of androgen deprivation therapy for prostate cancer: Can we do better? A retrospective observational analysis from a referral center. Oderda, M., Bertetto, O., Barbera, G., et al.[2023]

In a study of 1052 patients with metastatic castration-sensitive prostate cancer, apalutamide combined with androgen-deprivation therapy significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) compared to placebo plus ADT.

While apalutamide exposure did not correlate with improved survival outcomes, higher exposure levels were linked to an increased risk of skin rash and pruritus, suggesting that dose adjustments may be beneficial to manage these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety exposure-response relationships of apalutamide in patients with metastatic castration-sensitive prostate cancer: results from the phase 3 TITAN study. T'jollyn, H., Ackaert, O., Chien, C., 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]

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 phase 3 trial with 1052 patients suffering from metastatic, castration-sensitive prostate cancer, the addition of apalutamide to androgen-deprivation therapy (ADT) significantly improved radiographic progression-free survival, with 68.2% of patients in the apalutamide group remaining progression-free at 24 months compared to 47.5% in the placebo group.

Overall survival was also enhanced with apalutamide, showing 82.4% survival at 24 months versus 73.5% in the placebo group, while the side effects were similar between both groups, indicating that apalutamide is a safe and effective addition to ADT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. Chi, KN., Agarwal, N., Bjartell, A., et al.[2019]

References

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

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

2. 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]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Efficacy and safety of apalutamide in Japanese patients with nonmetastatic castration-resistant prostate cancer: a subgroup analysis of a randomized, double-blind, placebo-controlled, Phase-3 study. [2022]

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

Apalutamide efficacy, safety and wellbeing in older patients with advanced prostate cancer from Phase 3 randomised clinical studies TITAN and SPARTAN. [2023]

5. 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]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Profiling of Skeletal Muscle and Adipose Tissue Depots in Men with Advanced Prostate Cancer Receiving Different Forms of Androgen Deprivation Therapy. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Appropriateness and complications of androgen deprivation therapy for prostate cancer: Can we do better? A retrospective observational analysis from a referral center. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety exposure-response relationships of apalutamide in patients with metastatic castration-sensitive prostate cancer: results from the phase 3 TITAN study. [2022]

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

Apalutamide: First Global Approval. [2019]

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

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

11. United States pubmed.ncbi.nlm.nih.gov

Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. [2019]