Apalutamide + ADT for Prostate Cancer

(TITAN Trial)

Not currently recruiting at 304 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Aragon Pharmaceuticals, Inc.

Must be taking: ADT

Must not be taking: Anti-androgens, CYP17 inhibitors

Disqualifiers: Brain metastases, Visceral metastases, 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: Up to 35 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding apalutamide to standard hormone therapy (ADT) is more effective for men with metastatic hormone-sensitive prostate cancer (mHSPC). The researchers aim to determine if this combination can help patients live longer without cancer progression. Participants will receive either apalutamide with ADT or a placebo with ADT. The trial seeks men diagnosed with prostate cancer that has spread to the bones and who have previously responded well to treatments like docetaxel. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does exclude participants who have taken certain prostate cancer treatments or medications that affect seizures.

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

Research has shown that the combination of apalutamide and androgen deprivation therapy (ADT) is generally safe. In earlier studies, this treatment proved safe. For instance, in a study with patients who have hormone-sensitive prostate cancer, this combination helped patients live longer without their cancer worsening, indicating that the treatment did not cause significant harm, as patients continued taking it.

Another study found that using apalutamide with ADT improved survival rates without causing major side effects. While no treatment is risk-free, evidence suggests that any side effects are manageable and the treatment is relatively safe for most patients. It is important to consult a healthcare professional to understand what this might mean personally. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Apalutamide combined with Androgen Deprivation Therapy (ADT) for prostate cancer because it offers a novel approach to treatment. Unlike traditional therapies that primarily focus on lowering testosterone levels, Apalutamide is an androgen receptor inhibitor that prevents cancer cells from using androgens to grow. This dual-action method could potentially enhance treatment efficacy and delay disease progression. Additionally, the use of a placebo arm alongside ADT helps in assessing the true impact of Apalutamide, providing clearer insights into its benefits over standard treatments.

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

In this trial, participants will receive either apalutamide with androgen deprivation therapy (ADT) or a placebo with ADT. Research has shown that combining apalutamide with ADT can significantly improve outcomes for prostate cancer patients. Studies have found that this combination lowers the risk of death compared to other treatments and reduces levels of prostate-specific antigen (PSA), a protein associated with prostate cancer growth. Apalutamide with ADT extends the time before the cancer worsens. Overall, this treatment combination is associated with better survival rates for those with metastatic hormone-sensitive prostate cancer. ^{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 metastatic hormone-sensitive prostate cancer (mHSPC) who are fit for treatment (ECOG PS 0 or 1), have bone lesions confirmed by scans, and may have had limited prior treatments like docetaxel or ADT. Not eligible if they've had certain other cancers within 5 years, brain metastases, only lymph node involvement, visceral-only metastases, previous next-gen anti-androgens or seizure history.

Inclusion Criteria

I have had treatments for prostate cancer that met certain criteria.

I have specific details about my docetaxel treatment, including the number of cycles, last dose timing, and how my cancer responded.

My cancer has spread to my bones, confirmed by scans.

Exclusion Criteria

I have a history of seizures or take medication that could lower my seizure threshold.

My cancer has spread only to my internal organs.

My cancer has spread only to my lymph nodes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive apalutamide or placebo with ADT in 28-day cycles until disease progression or unacceptable toxicity

Up to 35 months

End of Treatment

Participants are monitored for safety and any adverse effects for 30 days after the last dose of study drug

4 weeks

Survival Follow-up

Participants are monitored for overall survival and other outcomes

Up to 57 months

Open-label Extension (optional)

Participants may opt into continuation of treatment with apalutamide for approximately 3 years if the study results are positive

36 months

Long-term Extension (optional)

Participants may continue receiving apalutamide if they derive benefit from treatment

What Are the Treatments Tested in This Trial?

Interventions

• Androgen Deprivation Therapy (ADT)
• Apalutamide
• Placebo

Trial Overview

The trial is testing whether adding a drug called Apalutamide to standard Androgen Deprivation Therapy (ADT) can help improve survival without the cancer getting worse on scans. Participants will either receive Apalutamide plus ADT or a placebo plus ADT to compare outcomes.

How Is the Trial Designed?

Group I: Placebo plus ADT Experimental Treatment 2 Interventions

Participants will receive matching Placebo with ADT.

Group II: Apalutamide plus ADT Experimental Treatment 2 Interventions

Participants will receive apalutamide 240 milligram (mg) (4X 60 mg tablets) with ADT.

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?

Aragon Pharmaceuticals, Inc.

Lead Sponsor

Trials

17

Recruited

5,400+

Published Research Related to This Trial

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 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]

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]

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]

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 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 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 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]

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 ( ...