Apalutamide + ADT for Prostate Cancer

(PROTEUS Trial)

Not currently recruiting at 314 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding a drug called apalutamide to standard hormone therapy (androgen deprivation therapy, or ADT) can more effectively treat high-risk prostate cancer that hasn't spread far. Researchers aim to determine if this combination improves surgery outcomes and prevents cancer spread better than hormone therapy alone. Men with prostate cancer who haven't received prior cancer treatments and meet specific criteria, such as a certain Gleason Score (a measure of cancer aggressiveness), may qualify. Participants will receive either the drug combination or a placebo with ADT before and after surgery. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in prostate cancer treatment.

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.

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

Research has shown that combining apalutamide with androgen deprivation therapy (ADT) is generally safe. One study demonstrated that this combination improved survival rates for prostate cancer patients and was well-tolerated. Another study found that patients using apalutamide and ADT experienced a significant slowdown in cancer progression, with no major side effects. Although all treatments can have side effects, current research suggests that apalutamide with ADT is generally safe. However, individual experiences can differ, so discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about Apalutamide + ADT for prostate cancer because it offers a more targeted approach compared to traditional treatments like standard ADT alone or chemotherapy. Apalutamide is an androgen receptor inhibitor that works by blocking the effects of androgens, which are hormones that can promote the growth of prostate cancer cells. This mechanism potentially makes Apalutamide more effective in slowing down or stopping cancer progression. Additionally, the combination of Apalutamide with ADT may enhance the overall effectiveness of the treatment, providing a comprehensive strategy to manage the disease.

What evidence suggests that apalutamide plus ADT could be an effective treatment for prostate cancer?

In this trial, participants will receive either a combination of apalutamide with androgen deprivation therapy (ADT) or a placebo with ADT. Research has shown that combining apalutamide with ADT significantly lowers the risk of death in prostate cancer patients compared to other treatments. Studies have found that this combination improves survival chances for those with prostate cancer that has spread and still responds to hormones. Apalutamide also helped many patients reach undetectable levels of PSA, a marker for prostate cancer, and slowed the disease's progression. This treatment has shown promising results in reducing signs of prostate cancer and improving survival, offering a strong potential benefit for those at high risk. ^{1 2 4 5 6}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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. A LTE may be initiated at sponsor's discretion after completion of the primary endpoint analysis.

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. A Long-Term Extension (LTE) may be initiated at sponsor's discretion after completion of the primary endpoint analysis.

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+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

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

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

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

Published Research Related to This Trial

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 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 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 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]

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]

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 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]

Citations

1. 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– ...

2. jnj.com jnj.com/media-center/press-releases/phase-2-data-for-erleada-apalutamide-plus-androgen-deprivation-therapy-following-radical-prostatectomy-in-patients-with-high-risk-localized-prostate-cancer-show-100-biochemical-free-recurrence-rate-more-than-two-years-post-surgery

Phase 2 data for ERLEADA® (apalutamide) plus androgen ... The treatment regimen demonstrated a serum testosterone recovery (≥150 ng/dL) rate of 76.4% at 12 months (95% CI, 65.0–84.5). The safety profile ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12346201/

Apalutamide Monotherapy in Metastatic Hormone-Sensitive ... Even in this trial, Apalutamide reduced PSA levels in about 90% of patients (compared to 2% of placebo group) and a ≥90% PSA reduction or ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1903307

Apalutamide for Metastatic, Castration-Sensitive Prostate ... Apalutamide plus ADT also resulted in a higher percentage of patients in whom undetectable PSA levels were achieved and a longer time to PSA progression than ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e17088

Apalutamide in patients with metastatic hormone-sensitive ... The combination of androgen deprivation therapy (ADT) and apalutamide has improved survival outcomes for patients with metastatic hormone-sensitive prostate ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35366072/

results from the phase 3 TITAN study Results: Apalutamide + ADT treatment was efficacious in extending rPFS and OS versus placebo + ADT. Within a relatively narrow apalutamide exposure range ( ...