What side effects are associated with this type of intervention?

Common treatments for prostate cancer, such as Apalutamide (an androgen receptor inhibitor) combined with GnRH agonists (which reduce testosterone production), have a range of side effects. Apalutamide can cause fatigue, hypertension, rash, diarrhea, and falls, while GnRH agonists are associated with hot flashes, decreased libido, erectile dysfunction, osteoporosis, and an increased risk of acute kidney injury. Combining these treatments may lead to a compounded side effect profile, requiring careful monitoring and management.

What prior FDA approvals exist?

The FDA has approved several treatments for prostate cancer that are similar to the combination of Apalutamide (an androgen receptor inhibitor) and GnRH agonists (which reduce testosterone production). Notable androgen receptor inhibitors include Enzalutamide and Darolutamide, which, like Apalutamide, block the androgen receptor signaling pathway. GnRH agonists such as Leuprolide and Goserelin are commonly used to lower testosterone levels. These treatments are often used in combination to enhance efficacy, particularly in advanced or castration-resistant prostate cancer.

What other types of research exist?

Promising alternatives to Apalutamide plus GnRH agonist for prostate cancer treatment in 2024 include: 1) Bicalutamide plus LHRH-A, which has shown better tolerability and similar efficacy compared to flutamide. 2) Enzalutamide plus ADT, which is effective for castration-resistant prostate cancer. 3) Bipolar Androgen Therapy (BAT), which may restore sensitivity to other treatments like enzalutamide and abiraterone. These alternatives offer different benefits and should be discussed with a healthcare provider to determine the best option based on individual patient needs.

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Androgen Receptor Inhibitor

Apalutamide + Hormone Therapy for Prostate Cancer

Q: What is the mechanism of action of this treatment?

Prostate cancer treatments often target the androgen pathway, crucial for prostate cancer cell growth. Androgen receptor inhibitors like Apalutamide block the androgen receptor, preventing testosterone from stimulating cancer cells. GnRH agonists reduce testosterone production by initially stimulating and then downregulating the release of gonadotropins from the pituitary gland. This dual approach is significant for prostate cancer patients as it effectively reduces the hormonal signals that drive cancer progression, potentially improving outcomes and delaying metastasis.

Phase 3

Waitlist Available

Research Sponsored by Aragon Pharmaceuticals, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) grade of 0 or 1

Age >= 18 years

Must not have

Bilateral orchiectomy

Prior treatment with enzalutamide, abiraterone acetate, orteronel, galeterone, ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and progestational agents (including cyproterone acetate) for prostate cancer

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 108 months

Awards & highlights

Pivotal Trial

Summary

This trial tests whether combining apalutamide with another treatment helps men with high-risk prostate cancer undergoing radiation therapy. The treatment aims to block and reduce male hormones that fuel cancer growth, potentially preventing the cancer from spreading. Apalutamide has been developed for treating prostate cancer and has shown effectiveness.

Who is the study for?

Men over 18 with high-risk, localized or locally advanced prostate cancer who are set to receive primary radiation therapy. They must be in good health with a low Charlson index (<=3), able to swallow pills, and have normal liver function and adequate blood counts. Participants should not have had prior treatments for prostate cancer, no history of seizures or conditions that may cause them, and agree to use condoms.

What is being tested?

The trial is testing if adding apalutamide plus GnRH agonist to the standard radiation treatment improves survival without metastasis in men with high-risk prostate cancer. It compares this combination against placebo versions while all participants receive radiation therapy.

What are the potential side effects?

Apalutamide can cause fatigue, rash, joint pain, falls, fractures, hot flushes, diarrhea, nausea; it might also affect thyroid function. GnRH agonists typically lead to symptoms like hot flashes and reduced sexual interest due to lower testosterone levels.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or can carry out light work.

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I am 18 years old or older.

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I can swallow pills without any difficulty.

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My prostate cancer is aggressive based on its Gleason score and PSA levels.

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I am scheduled for initial radiation therapy for prostate cancer.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had both testicles surgically removed.

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I have previously been treated with specific hormone therapies for prostate cancer.

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I have had treatments like radiation drugs or immunotherapy for prostate cancer.

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I have not taken steroids for the past 4 weeks and do not need them long-term.

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I have been using opioid painkillers for more than 3 weeks (pills) or more than 7 days (other forms).

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I have a stomach or intestine condition that affects how my body absorbs food.

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I have a history of seizures or conditions that could lead to seizures.

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I have not had major surgery in the last 4 weeks.

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I am taking or have taken seizure medication.

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I am not allergic to apalutamide, bicalutamide, GnRH agonists, or their ingredients.

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I have had radiation therapy to my pelvic area.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 108 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~108 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 108 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Metastasis-free Survival

Secondary study objectives

Event-free Survival on Conventional Imaging

Event-free Survival on Conventional Imaging or PSMA-PET Imaging

Metastasis-free Survival (MFS) on Conventional Imaging by Blinded Independent Central Review (BICR)

+5 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: ApalutamideExperimental Treatment4 Interventions

Participants will receive apalutamide (240 mg), by mouth, once daily for overall 30 months, plus bicalutamide placebo, by mouth, once daily, for four months from randomization. All participants are treated with gonadotropin releasing hormone (GnRH) agonist for 30 months from randomization and radiation therapy to the prostate started at about 8 weeks after randomization.

Group II: Control groupActive Control4 Interventions

Participants will receive apalutamide placebo, by mouth, once daily for overall 30 months, plus bicalutamide (50 mg), by mouth, once daily, for four months from randomization. All participants are treated with gonadotropin releasing hormone (GnRH) agonist for 30 months from randomization and radiation therapy to the prostate started at about 8 weeks after randomization.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Apalutamide

2015

Completed Phase 2

~5750

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Prostate cancer treatments often target the androgen pathway, crucial for prostate cancer cell growth. Androgen receptor inhibitors like Apalutamide block the androgen receptor, preventing testosterone from stimulating cancer cells. GnRH agonists reduce testosterone production by initially stimulating and then downregulating the release of gonadotropins from the pituitary gland. This dual approach is significant for prostate cancer patients as it effectively reduces the hormonal signals that drive cancer progression, potentially improving outcomes and delaying metastasis.