Ribociclib and Bicalutamide in AR+ TNBC
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|ClinicalTrials.gov Identifier: NCT03090165|
Recruitment Status : Recruiting
First Posted : March 24, 2017
Last Update Posted : November 1, 2022
|Condition or disease||Intervention/treatment||Phase|
|Triple Negative Breast Cancer||Drug: ribociclib Drug: Bicalutamide||Phase 1 Phase 2|
This is a non-randomized, single arm, open label study of the combination of bicalutamide with ribociclib in subjects with advanced AR+ TNBC. Prior to enrollment on the phase II cohort, a phase I run-in study will be performed to ensure safety and tolerability of the combination of bicalutamide and ribociclib in subjects with advanced AR+ TNBC.
In both the phase I and phase II portions of the study, subjects will receive bicalutamide 150 mg orally, once daily, continuously on Day 1 to Day 28. Each cycle of treatment is 28 days.
In the phase I portion of the study, cohorts of subjects will receive ribociclib in escalated doses (see protocol) orally, once daily in a 28 day cycle. For the phase II portion, the RP2D dose of ribociclib will be based on the phase I run-in.
In the phase II cohort, a two week lead-in of bicalutamide monotherapy will occur before cycle 1 combination therapy (Day -14 to day -1). Then ribociclib will be added on day 1 of cycle 1. This lead-in will be for CTC androgen receptor analysis.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||37 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Masking Description:||Open Label|
|Official Title:||A Phase I/II, Single Arm, Non-randomized Study of Ribociclib (LEE011), a CDK 4/6 Inhibitor, in Combination With Bicalutamide, an Androgen Receptor (AR) Inhibitor, in Advanced AR+ Triple-negative Breast Cancer: Big Ten Cancer Research Consortium BRE15-024|
|Actual Study Start Date :||May 7, 2018|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||September 2024|
Experimental: Arm A - Phase I
Dose Escalation Cohort 1 will consist of 3-6 patients who will receive bicalutamide 150mg PO daily on days 1-28 of a 28 day cycle and ribociclib 400mg PO daily on days 1-21 of a 28 day cycle.
Cohort 2 will consist of 3-6 patients who will receive bicalutamide 150mg PO daily on days 1-28 of a 28 day cycle and ribociclib 400mg PO daily on days 1-28 of a 28 day cycle.
Cohort 3 will consist of 3-6 patients who will receive bicalutamide 150mg PO daily on days 1-28 of a 28 day cycle and ribociclib 600mg PO daily on days 1-21 of a 28 day cycle.
Experimental: Arm B - Phase II Investigational Treatment The maximum safe dose of ribociclib in combination with bicalutamide will be given to up to 25 patients.
Other Name: LEE011
Other Name: LEE011
- Phase I: Maximum Tolerated Dose [ Time Frame: D1 of treatment to end of cohort cycle (assessed at 28 days) ]Phase I: Maximum tolerated dose (MTD) for subjects receiving ribociclib and bicalutamide without experiencing dose-limiting toxicity(s) (DLT) per Common Terminology Criteria for Adverse Events (CTCAE) v4
- Phase II: Clinical benefit rate (CBR) of treatment combination [ Time Frame: D1 of treatment to end of 4 treatment cycles (assessed at 16 weeks) ]Compare sum of confirmed complete plus partial responses plus stable disease per response evaluation criteria in solid tumors (RECIST) 1.1 criteria
- Phase I: Objective Response Rate (ORR) [ Time Frame: 2 years ]The objective response rate is the proportion of all subjects with confirmed PR or CR according to RECIST 1.1, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).
- Phase I: Duration of Response [ Time Frame: 2 years ]Duration of overall response-the period measured from the time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since treatment started).
- Phase I: Assess Safety and Tolerability By summarizing counts and percentages grade 3-5 adverse events (NCI CTCAE Version 4) [ Time Frame: 2 years ]By summarizing counts and percentages grade 3-5 adverse events (NCI CTCAE Version 4)
- Phase I: Ribociclib pharmacokinetics [ Time Frame: 2 months ]Time points: Peak Plasma Concentration (Cmax) Pre dose and 2-hours post-dose (±15 min) pharmacokinetic samples will be collected on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 2 Day 15.
- Phase II: Progression Free Survival (PFS) [ Time Frame: 2 years ]PFS will be summarized using Kaplan-Meier estimates of the median survival times.
- Phase II: Objective Response Rate (ORR) [ Time Frame: 2 years ]by RECIST 1.1 on treatment with combination of bicalutamide and ribociclib in advanced AR+ TNBC
- Phase II: Overall Survival (OS) [ Time Frame: 5 years ]Overall survival is defined by the date of treatment initiation to date of death from any cause.
- Phase II: Estimate Duration of Response [ Time Frame: 2 years ]On treatment with combination of bicalutamide and ribociclib in advanced Androgen Receptor (AR)+ Triple Negative Breast Cancer (TNBC)
- Phase II: Evaluate Safety and Tolerability By summarizing counts and percentages grade 3-5 adverse events (NCI CTCAE Version 4) [ Time Frame: 2 years ]By summarizing counts and percentages grade 3-5 adverse events (NCI CTCAE Version 4)
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): NCT03090165
|Contact: Kari Wisinski, MD||608-265-1700 ext email@example.com|
|Contact: Ahran Lee||317-634-5842 ext firstname.lastname@example.org|
|United States, Illinois|
|University of Illinois Cancer Center||Recruiting|
|Chicago, Illinois, United States, 60612|
|Contact: Ayesha Zaidi 312-413-1902 email@example.com|
|Principal Investigator: Kent Hoskins, MD|
|United States, Michigan|
|Michigan State University||Completed|
|Lansing, Michigan, United States, 48910|
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey||Completed|
|New Brunswick, New Jersey, United States, 08903|
|United States, New York|
|University of Rochester Medical Center||Recruiting|
|Rochester, New York, United States, 14642|
|Contact: Chelsea Marsh 585-275-9040 firstname.lastname@example.org|
|Principal Investigator: Ruth O'Regan, MD|
|United States, Pennsylvania|
|Penn State Cancer Institute||Completed|
|Hershey, Pennsylvania, United States, 17033|
|United States, Wisconsin|
|University of Wisconsin||Recruiting|
|Madison, Wisconsin, United States, 53792|
|Contact: Cancer Connect 608-262-5223 email@example.com|
|Principal Investigator:||Kari Wisinski, MD||University of Wisconsin, Madison|