What side effects are associated with this type of intervention?

Abemaciclib, a CDK4/6 inhibitor, can cause side effects such as diarrhea, neutropenia, fatigue, and nausea. Darolutamide, an androgen receptor inhibitor, is associated with fewer central nervous system side effects compared to other similar agents like enzalutamide and apalutamide, but it can still cause fatigue, pain in extremities, and rash. Androgen Deprivation Therapy (ADT), which reduces androgen levels or blocks their effects, commonly leads to hot flashes, decreased libido, erectile dysfunction, osteoporosis, and an increased risk of cardiovascular events.

What prior FDA approvals exist?

The FDA has approved several treatments for prostate cancer that are similar to those being studied in the Abemaciclib and Darolutamide trial. Androgen receptor inhibitors like enzalutamide, apalutamide, and darolutamide have been approved for both metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). Androgen deprivation therapy (ADT), which includes treatments like Gonadotropin-Releasing Hormone (GnRH) antagonists and agonists, is a cornerstone in managing advanced prostate cancer. While CDK4/6 inhibitors like Abemaciclib are primarily used in breast cancer, their potential in prostate cancer is being explored in ongoing trials.

What other types of research exist?

Promising novel alternatives for prostate cancer treatment in 2024 include: <ol> <li>PARP Inhibitors (e.g., Olaparib, Rucaparib): These target DNA repair pathways and have shown efficacy in patients with specific genetic mutations (e.g., BRCA1/2).</li> <li>PSMA-Targeted Therapies (e.g., Lutetium-177 PSMA-617): These radioligand therapies target prostate-specific membrane antigen (PSMA) and have shown promising results in metastatic castration-resistant prostate cancer (mCRPC).</li> <li>Immunotherapy (e.g., Pembrolizumab): Immune checkpoint inhibitors are being explored for their potential to enhance the immune response against prostate cancer cells.</li> <li>Next-Generation Androgen Receptor Inhibitors (e.g., Apalutamide, Enzalutamide): These continue to be refined and may offer improved efficacy and safety profiles.</li> <li>Combination Therapies (e.g., combining PARP inhibitors with androgen receptor inhibitors): These are being investigated for their potential to provide synergistic effects and overcome resistance mechanisms.</li> </ol>

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Cyclin-Dependent Kinase Inhibitor

Darolutamide + Abemaciclib for Prostate Cancer

Phase 1 & 2

Waitlist Available

Led By Praful Ravi, MB BChir, MRCP

Research Sponsored by Praful Ravi

Eligibility Criteria Checklist

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

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at 2, 3, and 5 years.

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of two oral drugs, abemaciclib and darolutamide, with hormone therapy to treat advanced prostate cancer. It aims to find the safest and most effective dose. The study focuses on men with advanced or high-risk prostate cancer. The treatment works by blocking proteins that help cancer grow and reducing hormone levels that fuel the cancer.

Who is the study for?

Men over 18 with confirmed prostate adenocarcinoma, able to swallow pills and follow study rules. They must have a recent biopsy showing significant cancer presence without certain variants, no metastatic disease by specific scans, be candidates for surgical removal of the prostate, and have proper organ function. Contraception is required during and after the trial.

What is being tested?

The trial tests combining two oral drugs (abemaciclib and darolutamide) with standard hormone therapy for various stages of prostate cancer. The first phase will determine safe dosages before expanding into broader testing. About 93 participants will undergo treatment for six months followed by up to four-and-a-half years of monitoring.

What are the potential side effects?

Potential side effects include fatigue, digestive issues like nausea or diarrhea, blood cell count changes leading to increased infection risk or bleeding problems, liver function alterations, allergic reactions, and possibly others not yet known.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at 2, 3, and 5 years.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at 2, 3, and 5 years.

This trial's timeline: 3 weeks for screening, Varies for treatment, and at 2, 3, and 5 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

Phase 1 - Dose Limiting Toxicity (DLT)

Phase 1 - Maximum Tolerated Dose (MTD)

Phase 1 - Recommended Phase 2 Dose (RP2D)

+1 more

Secondary study objectives

Phase 1 & 2 - Grade 3 or Higher Treatment-Related Toxicity Rate

Phase 1 - Median Radiographic Progression-Free Survival (rPFS)

Phase 1 - Objective Response Rate (ORR)

+5 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: Phase 2 - Neoadjuvant Darolutamide, Ademaciclib, and ADT prior to Radical ProstatectomyExperimental Treatment5 Interventions

per protocol, for 6, 28-day cycles

Group II: Phase 2 - Neoadjuvant Darolutamide and ADT prior to Radical ProstatectomyExperimental Treatment4 Interventions

per protocol, for 6, 28-day cycles

Group III: Phase 1 Lead In in CRPCExperimental Treatment5 Interventions

Standard 3+3 dose escalation scheme with 3 dose levels of abemaciclib and a constant dose of darolutamide, per protocol, for 6, 28-day cycles

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Degarelix

2002

Completed Phase 3

~3730

Abemaciclib

2019

Completed Phase 2

~1890

Darolutamide

2018

Completed Phase 2

~100

Do I qualify?Apply below to find out

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 receptor signaling pathway, which is crucial for the growth and survival of prostate cancer cells. Androgen Deprivation Therapy (ADT) reduces androgen levels or blocks their effects, thereby slowing cancer progression. Darolutamide, an androgen receptor inhibitor, prevents androgens from binding to their receptors, further inhibiting cancer cell growth. Abemaciclib, a CDK4/6 inhibitor, disrupts the cell cycle, preventing cancer cells from proliferating. These mechanisms are vital as they directly interfere with the pathways that prostate cancer cells rely on, offering effective strategies to manage and treat the disease.