ADT + Apalutamide for Prostate Cancer

(LIBERTAS Trial)

Recruiting at 101 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

Disqualifiers: Seizure history, Heart conditions, 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

420 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to determine if the intermittent use of androgen-deprivation therapy (ADT) in participants with metastatic castrate-sensitive prostate cancer (mCSPC) who reached a prostate-specific antigen (PSA) level \< 0.2 nanograms/millilitres (ng/mL) after 6 months of treatment with apalutamide and ADT combination therapy provides non-inferior radiographic progression-free survival (rPFS) and a reduced burden of hot flashes measured as 18-month percent change in severity adjusted hot flash score.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination ADT + Apalutamide 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 better overall survival and progression-free survival with this combination compared to ADT alone. ^{1 2 3 4 5}

Is the combination of ADT and Apalutamide safe for humans?

The combination of ADT and Apalutamide (Erleada) has been studied in men with prostate cancer and is generally considered safe, with side effects similar to those of ADT alone. Common side effects of ADT include increased body fat and decreased muscle mass, while Apalutamide has been shown to maintain quality of life without significant additional safety concerns. ^{4 6 7 8 9}

How is the drug ADT + Apalutamide unique for treating prostate cancer?

ADT combined with Apalutamide is unique because it significantly improves survival outcomes in men with metastatic castration-sensitive prostate cancer by directly inhibiting the androgen receptor, which is crucial for cancer growth. This combination extends overall survival and delays the need for chemotherapy, while maintaining quality of life, making it a novel option compared to standard treatments. ^{1 2 3 4 10}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for individuals assigned male at birth with advanced prostate cancer that has spread, who can perform daily activities (with or without stable physical limitations), and have not planned to conceive. They must be able to swallow medication and should not have gastrointestinal issues affecting drug absorption, a history of seizures, recent severe heart conditions, or specific allergies.

Inclusion Criteria

I can care for myself and am up and about more than 50% of my waking hours, even if I have stable physical limitations not caused by my prostate cancer.

My prostate cancer has spread to 2 or more areas outside the prostate, confirmed by scans.

I have had surgery to remove both testicles or am on hormone therapy for gender transition.

Exclusion Criteria

I have a digestive condition that affects how my body absorbs food.

I haven't had severe heart issues or blood clots in the last 6 months.

You have a history of seizures or a condition that makes you more likely to have seizures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants receive apalutamide and ADT combination therapy for 6 months to reach a PSA level < 0.2 ng/mL

6 months

Main Treatment

Participants continue with either continuous or intermittent ADT with apalutamide, followed up for at least 18 months

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 3 years 9 months

Treatment Details

Interventions

• Androgen-deprivation Therapy (ADT)
• Apalutamide

Trial Overview The study tests if taking breaks from hormone therapy after initial treatment with apalutamide reduces the growth of prostate cancer without worsening symptoms like hot flashes compared to continuous treatment. Participants' PSA levels are monitored for changes.

Participant Groups

Group I: Arm B (Continuous ADT Group) Experimental Treatment 2 Interventions

Participants with PSA level \<0.2 ng/mL after 6 months of treatment with Apalutamide and ADT during initial treatment phase, will enter main treatment phase and continue to receive apalutamide plus ADT or followed up for at least 18 months from Day 1 of Cycle 7 (each cycle 28 days) or have discontinued the study, whichever occurs first.

Group II: Arm A (Intermittent ADT Group) Experimental Treatment 2 Interventions

Participants with PSA level \<0.2 ng/mL after 6 months of treatment with Apalutamide and ADT during initial treatment phase, will enter main treatment phase and treated with apalutamide with intermittent ADT per protocol or followed up for at least 18 months from Day 1 of Cycle 7 (each cycle 28 days) or have discontinued the study, whichever occurs first.

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

Approved in United States as Androgen-deprivation Therapy for:

• Prostate cancer
• Metastatic castrate-sensitive prostate cancer
• Non-metastatic castration-resistant prostate cancer

Approved in European Union as Androgen-deprivation Therapy for:

• Prostate cancer
• Metastatic castrate-sensitive prostate cancer
• Non-metastatic castration-resistant prostate cancer

Approved in Canada as Androgen-deprivation Therapy for:

• Prostate cancer
• Metastatic castrate-sensitive prostate cancer
• Non-metastatic castration-resistant 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 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]

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 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]

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]

Androgen deprivation therapy (ADT) is effective for managing metastatic or recurrent prostate cancer but can lead to significant side effects, including changes in body composition, increased fracture risk, and insulin resistance.

Recent studies suggest that denosumab and toremifene citrate can help reduce fracture risk in men undergoing ADT, highlighting the importance of managing these adverse effects to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen deprivation therapy in prostate cancer: anticipated side-effects and their management. Kim, HS., Freedland, SJ.[2015]

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 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. 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]

2. 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]

3. 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]

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

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

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

Androgen deprivation therapy in prostate cancer: anticipated side-effects and their management. [2015]

9. 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]

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

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