Enzalutamide With and Without Ribociclib for Metastatic, Castrate-Resistant, Chemotherapy-Naive Prostate Cancer That Retains RB Expression
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02555189|
Recruitment Status : Recruiting
First Posted : September 21, 2015
Last Update Posted : June 4, 2021
|Condition or disease||Intervention/treatment||Phase|
|Hormone-Resistant Prostate Cancer Metastatic Prostate Carcinoma Prostate Carcinoma Metastatic in the Bone Stage IV Prostate Cancer||Drug: Enzalutamide Drug: Ribociclib||Phase 1 Phase 2|
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)
I. PSA progression-free survival.
II. Radiographic progression-free survival.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||90 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Randomized Phase IB/II Study of Enzalutamide With and Without Ribociclib in Patients With Metastatic Castrate Resistant, Chemotherapy Naïve Prostate Cancer That Retains RB Expression|
|Actual Study Start Date :||December 1, 2015|
|Estimated Primary Completion Date :||July 2021|
|Estimated Study Completion Date :||September 2021|
Patients receive enzalutamide PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Experimental: Enzalutamide + Ribociclib
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.
Other Name: LEE011
- Dose limiting toxicity of Ribociclib (Phase IB) [ Time Frame: 28 days ]DLT is defined as an adverse event or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications. All analysis will be descriptive.
- Proportion of patients with a >= 50% reduction in PSA (Phase II) [ Time Frame: 12 weeks ]The proportion of subjects with 50% reduction in PSA at 12 weeks will be estimated within each group along with exact 95% binomial confidence intervals. Groups will be compared with respect to the proportion of subjects with a 50% reduction in PSA at 12 weeks using a one-sided Fisher's exact test with alpha=0.10. Summary statistics include the number of observations, mean, standard deviation, median, minimum, and maximum values. A P-value of 0.10 will be used to declare statistical significance for the primary outcome.
- PSA progression free survival (PFS) [ Time Frame: Time of first dose until progression (25% increase in PSA from nadir) or death, assessed up to 2 years ]Summarized by treatment arm using Kaplan-Meier plots. Median PFS will be estimated from the Kaplan-Meier analysis.
- Radiographic PFS (rPFS) [ Time Frame: Time from treatment start to disease progression in bone or soft-tissue, or death, whichever occurs first, assessed up to 2 years ]Summarized by treatment arm using Kaplan-Meier plots. Median rPFS will be estimated from the Kaplan-Meier analysis.
- Overall survival [ Time Frame: Up to 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02555189
|Contact: William Kevin Kelly, MD||215-955-8874|
|Contact: Clinical Trials Office||215-955-1661|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: David Smith, MD 734-763-6537|
|United States, New York|
|Roswell Park Cancer Institute||Recruiting|
|Buffalo, New York, United States, 14263|
|Contact: Gurkamal Chatta, MD Gurkamal.Chatta@RoswellPark.org|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Susan Slovin, MD, PhD 646-422-4470|
|United States, Pennsylvania|
|Thomas Jefferson University||Recruiting|
|Philadelphia, Pennsylvania, United States, 19107|
|Contact: William Kevin Kelly, MD 215-955-8874|
|Contact: Clinical Trials Office 215-955-1661|
|Principal Investigator: William Kevin Kelly, MD|
|Sub-Investigator: Robert Den, MD|
|Sub-Investigator: Jean Hoffman-Censits, MD|
|Sub-Investigator: Jianqing Lin, MD|
|Sub-Investigator: Leonard Gomella, MD|
|Sub-Investigator: Edouard Trabulsi, MD|
|Sub-Investigator: Costas Lallas, MD|
|Principal Investigator:||William Kevin Kelly, MD||Thomas Jefferson University|