Enzalutamide With Ribociclib in Treating Patients With Metastatic Castrate-Resistant, Chemotherapy Naive Prostate Cancer That Retains Retinoblastoma Expression

Metastatic Prostate Carcinoma Clinical Trial

Official title: Phase IB/II Study of Enzalutamide With Ribociclib in Patients With Metastatic Castrate Resistant, Chemotherapy Naïve Prostate Cancer That Retains RB Expression

Status Completed

Clinical Trial Summary

This phase Ib/II trial studies the safety, side effects, best dose, and effectiveness of ribociclib when given with enzalutamide in treating patients with castrate-resistant prostate cancer that has spread from the primary site (place where it started) to other places in the body (metastatic), is chemotherapy naive, 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. Enzalutamide with ribociclib may be safe, tolerable and/or effective in treating metastatic, castrate-resistant, chemotherapy naive prostate cancer that retains retinoblastoma expression.

Clinical Trial 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 (rPFS). III. Safety. IV. Pharmacokinetics.

CORRELATIVE/EXPLORATORY/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.

Patients receive enzalutamide orally (PO) once daily (QD) on days 1-28 and ribociclib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, tumor biopsy, echocardiography (ECHO) or multigated acquisition scan (MUGA), bone scan, and computed tomography (CT) or magnetic resonance imaging (MRI) on study.

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

Related Conditions & MeSH terms

• Carcinoma
• Castration-Resistant Prostate Carcinoma
• Metastatic Prostate Carcinoma
• Prostate Carcinoma Metastatic in the Bone
• Prostatic Neoplasms
• Stage IV Prostate Cancer AJCC v7

• NCT number: NCT02555189
• Study type: Interventional
• Source: Thomas Jefferson University
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 1, 2015
• Completion date: September 1, 2023