What is the mechanism of action of this treatment?

Common treatments for prostate cancer, such as apalutamide, enzalutamide, and abiraterone, primarily target the androgen receptor pathway. Apalutamide and enzalutamide are androgen receptor inhibitors that block the binding of androgens to the receptor, inhibit the receptor's movement into the cell nucleus, and prevent its interaction with DNA. Abiraterone, on the other hand, inhibits the enzyme CYP17A1, which is involved in androgen production. These mechanisms are vital for prostate cancer patients as they disrupt the androgen signaling that drives cancer cell growth, thereby delaying disease progression and improving survival outcomes.

What side effects are associated with this type of intervention?

Common treatments for prostate cancer, particularly androgen receptor inhibitors like apalutamide, enzalutamide, and darolutamide, have several known side effects. Apalutamide and enzalutamide can cause fatigue, hypertension, and a higher risk of seizures, with enzalutamide having a slightly higher incidence of central nervous system toxicities. Darolutamide, due to its lower blood-brain barrier penetration, tends to have fewer central nervous system side effects but can still cause fatigue and hypertension. Androgen deprivation therapy (ADT) commonly leads to hot flashes, decreased libido, and osteoporosis. Chemotherapy agents like docetaxel can cause neutropenia, fatigue, and peripheral neuropathy.

What prior FDA approvals exist?

The FDA has approved several androgen receptor inhibitors for the treatment of prostate cancer. Apalutamide was approved for metastatic castration-sensitive prostate cancer (CSPC) based on studies showing improved overall survival and radiographic progression-free survival. Enzalutamide, another androgen receptor inhibitor, has been approved for both metastatic castration-resistant prostate cancer (CRPC) and nonmetastatic CRPC, demonstrating benefits in overall survival and progression-free survival. Darolutamide, also an androgen receptor inhibitor, has been approved for nonmetastatic CRPC, showing improved metastasis-free survival. These approvals highlight the effectiveness of androgen receptor inhibitors in managing various stages of prostate cancer.

What other types of research exist?

Promising alternatives to Apalutamide for prostate cancer patients include Enzalutamide and Darolutamide. Enzalutamide has shown efficacy in both metastatic hormone-sensitive and castration-resistant prostate cancer. Darolutamide is effective in nonmetastatic castration-resistant prostate cancer and has shown promise in treating enzalutamide-resistant cases. Both drugs have been evaluated in clinical trials and are considered effective options.

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LHRH Agonist

Apalutamide + Radiotherapy for Prostate Cancer (PRIMORDIUM Trial)

Phase 3

Waitlist Available

Research Sponsored by Janssen Pharmaceutica N.V., Belgium

Eligibility Criteria Checklist

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

Must have

Be able to swallow whole the study drug tablets or follow the instructions for admixing with apple sauce

Biochemically recurrent prostate cancer after RP with a high risk of developing metastasis defined as pathological Gleason score greater than or equal to (>=) 8 evaluated from prostate tissue specimen at radical prostatectomy, OR PSADT less than or equal to (<=) 12 months at the time of screening

Must not have

Previous treatment with androgen deprivation therapy (ADT) for prostate cancer

History of pelvic radiation for malignancy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 9 years

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial is testing if adding a new medication to standard prostate cancer treatments can better delay the spread of cancer or death. The combination works by blocking male hormones, killing cancer cells, and lowering hormone levels.

Who is the study for?

Men with high-risk, hormone-sensitive prostate cancer who've had a prostatectomy and show no signs of metastasis. They must have a PSA <0.1 ng/mL post-surgery, good performance status (able to carry out daily activities), and be at high risk for metastasis based on specific criteria like Gleason score or PSADT. Participants need to swallow pills and undergo PSMA-PET scans.

What is being tested?

The trial is testing if adding Apalutamide to standard treatment with Radiotherapy plus LHRH agonist can delay the spread of cancer or death in men with high-risk prostate cancer. The effectiveness will be measured using advanced imaging techniques like PSMA-PET.

What are the potential side effects?

Apalutamide may cause fatigue, rash, joint pain, falls, fractures, diarrhea, hot flushes, decreased appetite and weight loss among other side effects. Side effects from radiotherapy include skin irritation at the treated site and fatigue.

Eligibility Criteria

Inclusion Criteria

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

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I can swallow pills whole or mix them with apple sauce.

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My prostate cancer has returned after surgery, with a high risk of spreading.

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My prostate cancer was confirmed through a tissue examination.

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I am fully active or can carry out light work.

Exclusion Criteria

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

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I have been treated with hormone therapy for prostate cancer.

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I have had radiation treatment for cancer in my pelvic area.

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I am allergic or react badly to apalutamide, LHRH agonists, or their ingredients.

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I have had chemotherapy for prostate cancer.

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My scans show prostate cancer has spread.

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I have previously been treated with medications or surgery to lower my androgen levels.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 9 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 9 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 9 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Prostate specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) Metastatic Progression-free Survival (ppMPFS)

Secondary study objectives

Number of Participants With Adverse Event (AE) and Serious Adverse Events (SAEs)

Overall Survival

PSA Levels at Week 26

+4 more

Awards & Highlights

Pivotal Trial

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

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Interventional Cohort (Group 2): RT+LHRHa + ApalutamideExperimental Treatment3 Interventions

Participants will receive prostate-bed plus pelvic lymph node salvage external-beam radiotherapy (RT) with or without optional stereotactic body radiation therapy (SBRT), along with a LHRHa as a 3-monthly depot preparation within 3 days after randomization and the end of Week 12, or as a 6-monthly depot preparation within 3 days after randomization. Participants will also receive 240 milligram (mg) of apalutamide starting within 3 days after randomization as film-coated tablets, to be swallowed whole and together once daily with or without food, for a period of 180 Days.

Group II: Interventional Cohort (Group 1): RT+ LHRHaActive Control2 Interventions

Participants will receive radiotherapy (RT) which is defined as prostate-bed plus pelvic lymph node salvage external-beam radiotherapy with or without optional stereotactic body radiation therapy (SBRT), along with a luteinizing hormone-releasing hormone agonist (LHRHa) as a 3-monthly depot preparation within 3 days after randomization and the end of Week 12, or as a 6-monthly depot preparation within 3 days after randomization.

Group III: Observational Cohort(Group3) PSMA-PET Negative ParticipantsActive Control1 Intervention

Enrollment into this cohort will be stopped further. Participants who were PSMA-PET-negative at screening and were already enrolled in the Observational Cohort will continue in this cohort. Data collected in the course of routine clinical practice during this period will include clinical evaluations, disease progression, therapies administered as per standard-of-care at the study-sites and survival status. For Observational Cohort, information will be entered into the electronic case report form (eCRF) from the medical records at least twice a year. The use of any medicinal product(s) for the treatment and management of participants will be at discretion of the treating physician.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Radiotherapy

2017

Completed Phase 3

~2610

LHRHa

2013

Completed Phase 2

~140

Apalutamide

2015

Completed Phase 2

~5750

0 / 10Eligibility 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

Common treatments for prostate cancer, such as apalutamide, enzalutamide, and abiraterone, primarily target the androgen receptor pathway. Apalutamide and enzalutamide are androgen receptor inhibitors that block the binding of androgens to the receptor, inhibit the receptor's movement into the cell nucleus, and prevent its interaction with DNA. Abiraterone, on the other hand, inhibits the enzyme CYP17A1, which is involved in androgen production. These mechanisms are vital for prostate cancer patients as they disrupt the androgen signaling that drives cancer cell growth, thereby delaying disease progression and improving survival outcomes.