Last updated on March 2019

Enzalutamide With and Without Ribociclib for Metastatic Castrate-Resistant Chemotherapy-Naive Prostate Cancer That Retains RB Expression


Brief description of study

This partially randomized phase IB/II trial studies the side effects and best dose of ribociclib when given with enzalutamide and to see how well they work compared to enzalutamide alone in treating patients with prostate cancer that does not respond to treatment with hormones (hormone resistant), has spread from the primary site (place where it started) to other places in the body (metastatic), is chemotherapy nave, and retains retinoblastoma expression. Testosterone can cause the growth of prostate cancer cells. Hormone therapy using enzalutamide may fight prostate cancer by blocking the use of testosterone by the tumor cells. Ribociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether enzalutamide works better when given with or without ribociclib in treating patients with prostate cancer.

Detailed Study Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of ribociclib in combination with 160 mg of enzalutamide. (Phase Ib)

II. To determine efficacy with respect to the proportion of subjects that achieve a >= 50% reduction in prostate-specific antigen (PSA) at 12 weeks. (Phase II)

SECONDARY OBJECTIVES:

I. PSA progression-free survival.

II. Radiographic progression-free survival.

III. Safety.

IV. Pharmacokinetics.

TERTIARY OBJECTIVES:

I. To evaluate the expression of retinoblastoma (RB) in circulating tumor cells (CTCs) and tumor tissue.

II. To evaluate other mechanisms of castrate resistance (such as androgen receptor [AR]-variant [v]7) in tumor tissue and CTCs.

III. To explore resistance mechanisms of cyclin dependent kinase (CDK)4/6 inhibitors in tumor samples in patients that progress on enzalutamide and ribociclib.

IV. Explore the use/correlation of circulating deoxyribonucleic acid (DNA)/exosomes in castrate-resistant prostate cancer (CRPC) patients treated with enzalutamide with and without ribociclib.

V. Androgen profiles and correlation to clinical outcomes. VI. Development of model explant systems to correlate with the clinical outcome.

OUTLINE: This is a phase I, dose-escalation study of ribociclib followed by a phase II study.

PHASE Ib: Patients receive enzalutamide orally (PO) once daily (QD) on days 1-28 and ribociclib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive enzalutamide PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive enzalutamide PO QD on days 1-28 and ribociclib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 24 months.

Clinical Study Identifier: NCT02555189

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Recruitment Status: Open


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