ADT + Apalutamide for Prostate Cancer

(LIBERTAS Trial)

Not currently recruiting at 126 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if using hormone therapy (androgen-deprivation therapy, or ADT) less frequently can be as effective as continuous use for men with metastatic castrate-sensitive prostate cancer. It also examines whether this approach can reduce hot flashes, a common side effect. Participants will receive a combination of ADT and another drug called apalutamide (also known as Erleada). Those with confirmed prostate cancer who have experienced a drop in prostate-specific antigen (PSA) levels after initial treatment might be suitable candidates. 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 whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that apalutamide, when combined with androgen-deprivation therapy (ADT), is generally safe for treating prostate cancer. Studies have found apalutamide to be effective and well-tolerated by patients. For instance, a large study reported that only a small number of patients (0.2%) experienced serious side effects, such as problems with blood flow to the brain. Another study confirmed apalutamide's safety in both clinical trials and everyday use.

ADT, often used with apalutamide, is a common treatment for prostate cancer. It works by lowering the levels of male hormones that can help cancer grow. While ADT is effective, it can cause side effects like hot flashes and tiredness, but these are usually manageable.

Since this trial is in a later stage, the treatments have already passed initial safety checks, providing more information about their safety. Overall, apalutamide with ADT is considered well-tolerated, and many patients do not experience severe side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for prostate cancer involve continuous androgen-deprivation therapy (ADT) to lower testosterone levels, which can fuel cancer growth. However, the unique aspect of this study is the comparison between continuous ADT and intermittent ADT when used with Apalutamide, a medication that blocks the effect of androgens. Researchers are excited because intermittent ADT could potentially reduce side effects and improve quality of life without compromising effectiveness. Apalutamide, when combined with ADT, offers a dual mechanism by both lowering androgen levels and blocking their action, presenting a promising approach for managing prostate cancer. This trial aims to find out if this new protocol could be a more patient-friendly option while still effectively controlling the disease.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that apalutamide, when combined with hormone therapy (ADT), effectively treats prostate cancer that has spread and still responds to hormone treatment. Studies have found that this combination significantly improves survival rates. For instance, after 48 months, 65.1% of patients taking apalutamide with hormone therapy were alive, compared to 51.8% of those taking a placebo with hormone therapy. Additionally, apalutamide was linked to a 23% lower risk of death at 24 months compared to other treatments. In this trial, participants will be divided into two groups: one receiving continuous ADT with apalutamide and the other receiving intermittent ADT with apalutamide. These findings highlight the potential of apalutamide and hormone therapy in improving outcomes for patients with this type of prostate cancer. ^{6 7 8 9 10}

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?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: 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) and followed up for up to a maximum of 2 years after the main treatment phase, or until death, withdrawal of consent, loss to follow-up, early termination of the study by the sponsor for any reason, whichever occurs first.

Group II: Arm B (Continuous ADT Group) Active Control 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) and followed up for up to a maximum of 2 years after the main treatment phase, or until death, withdrawal of consent, loss to follow-up, early termination of the study by the sponsor for any reason, 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+

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

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 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]

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]

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]

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]

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]

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]

Citations

1. jnj.com jnj.com/media-center/press-releases/erleada-apalutamide-demonstrates-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-compared-to-enzalutamide-in-patients-with-metastatic-castration-sensitive-prostate-cancer

ERLEADA® (apalutamide) demonstrates statistically ... Largest head-to-head real-world study in mCSPC demonstrated that ERLEADA® reduced risk of death by 23 percent at 24 months compared to ...

2. erleadahcp.com erleadahcp.com/efficacy/

Efficacy | ERLEADA® (apalutamide) HCP Median follow-up time was 44.0 months. 1. The survival rate at 48 months was 65.1% for ERLEADA ® + ADT patients vs 51.8% for placebo + ADT patients.

3. 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– ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39613567/

Results from the Multicenter Real-world ARON-3 Study Our results show that apalutamide is a safe and effective drug in the real-world setting as well as in clinical trials.

5. urotoday.com urotoday.com/video-lectures/mhspc/video/mediaitem/4763-real-world-data-explores-benefits-of-apalutamide-in-metastatic-hormone-sensitive-prostate-cancer-benjamin-maughan.html

Real-World Data Explores Benefits of Apalutamide in ... All doublet combinations showed superior outcomes compared to ADT monotherapy, with apalutamide demonstrating numerically superior results. Dr.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4094624/

Androgen deprivation therapy for prostate cancer: long-term ... ADT can normalize serum prostate specific antigen in over 90% of patients and results in sizable tumor response in 80% to 90%. This treatment can be done either ...

7. cancer.gov cancer.gov/types/prostate/prostate-hormone-therapy-fact-sheet

Hormone Therapy for Prostate Cancer Fact Sheet - NCI Hormone therapies, which are treatments that decrease androgen levels or block androgen action, can inhibit the growth of such prostate cancers.

8. ascopubs.org ascopubs.org/doi/10.1200/EDBK_433126

Balancing Hormone Therapy: Mitigating Adverse Effects of ... Treatment advances including ADT have led to improvements in PCa management and survival, with trials reporting median survival of over 6 years ...

9. openurologyandnephrologyjournal.com openurologyandnephrologyjournal.com/VOLUME/17/ELOCATOR/e1874303X237036/FULLTEXT/

6-month Formulations of Androgen Deprivation Therapy for ... A recent analysis found a high non-adherence rate of 84% for LHRH agonist injections based on dosing schedules used in pivotal trials. Method:.

10. cancer.org cancer.org/cancer/types/prostate-cancer/treating/hormone-therapy.html

Hormone Therapy for Prostate Cancer Lowering androgen levels or stopping them from getting into prostate cancer cells can often make prostate cancers shrink or grow more slowly for ...