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 BTCRC-BRE15-024

Description
This is an open label, multi-institutional, single arm phase II trial of ribociclib in combination with bicalutamide in advanced AR+ triple-negative breast cancer. No randomization or blinding is involved.

Objective
Primary Outcome Measures:

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)

Treatment 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.

Key Eligibility For full study eligibility, please see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Breast

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital