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 : June 6, 2018
|Condition or disease||Intervention/treatment||Phase|
|Triple Negative Breast Cancer||Drug: ribociclib Drug: Bicalutamide||Phase 1 Phase 2|
OUTLINE: This is a multi-center study.
- bicalutamide - 150mg po daily D1 - D28 (Cycle = 28 days)
- ribociclib po daily D1 - D21 of 28 day cycle
PHASE I SAFETY RUN-IN COHORT:
The maximum tolerated dose (MTD) of bicalutamide in combination with ribociclib will be determined using a standard "3+3" design. The first cohort of 3 subjects will receive ribociclib 400mg po daily D1 - D21 of a 28 day cycle (Dose Level 1). If no DLTs are experienced then the next cohort of 3 subjects will receive ribociclib 400mg po daily D1 - D28 of a 28 day cycle (Dose Level 2). If no DLTs are experienced then the next cohort of 3 subjects will receive ribociclib 600mg po daily D1 - D21 of a 28 day cycle (Dose Level 3). If no DLTs are experienced on Dose Level 3, then 3 additional subjects should be treated at this level before declaring MTD.
DLTs will be assessed within the first cycle (28 days).
PHASE II INVESTIGATIONAL TREATMENT:
- co-therapy bicalutamide 150mg po daily D1 - D28
- ribociclib po at the RP2D as determined in the Phase I Safety Run-In Cohort
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 28 days prior to registration
Life expectancy of > 12 weeks as determined by the treating physician.
- White blood cell (WBC) ≥4 × 10^9/L
- Absolute Neutrophil Count (ANC) ≥1.5 × 10^9/L
- Hemoglobin (Hb) ≥9 g/dL
- Platelets (Plt) ≥100 × 10^9/L
- Creatinine ≤1.5 mg/dL OR
- Calculated creatinine clearance ≥50 ml/min using the Cockcroft-Gault formula
- Bilirubin ≤upper limit of normal (ULN)*
- Aspartate aminotransferase (AST) ≤2.5 × ULN or ≤5 × ULN if liver mets.
- Alanine aminotransferase (ALT) ≤2.5 × ULN or ≤5 × ULN if liver mets. * For subjects with Gilbert's syndrome, this will apply to direct bilirubin only.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||58 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 :||March 2, 2017|
|Estimated Primary Completion Date :||September 2018|
|Estimated Study Completion Date :||September 2019|
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 46 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: Clinical Benefit Rate (CBR) at 16 weeks based on degree of Androgen Receptor (AR) expression by Immunohistochemistry (IHC) [ Time Frame: 16 weeks ]CBR at 16 weeks based on degree of AR expression by IHC (AR >0% vs. AR ≥10%).
- Phase II: Progression Free Survival (PFS) based on degree of AR expression by IHC [ Time Frame: 2 years ]PFS based on degree of AR expression by IHC (AR >0% vs. AR ≥10%).
- 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: Dana Musapatika||317.634.5842 ext email@example.com|
|Contact: Ruth O'Regan, M.D.||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||Recruiting|
|Lansing, Michigan, United States, 48910|
|Contact: Karen Luellen 517-975-9534 firstname.lastname@example.org|
|Principal Investigator: Deimante Tamkus, MD|
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey||Recruiting|
|New Brunswick, New Jersey, United States, 08903|
|Contact: Alison Haegler 732-235-8060 email@example.com|
|Principal Investigator: Nancy Chan, MD|
|United States, Pennsylvania|
|Penn State Cancer Institute||Recruiting|
|Hershey, Pennsylvania, United States, 17033|
|Contact: Sean Flemings 717-531-5364 firstname.lastname@example.org|
|Principal Investigator: Cristina Truica, MD|
|United States, Wisconsin|
|University of Wisconsin||Recruiting|
|Madison, Wisconsin, United States, 53792|
|Contact: Cancer Connect 608-262-5223 email@example.com|
|Study Chair:||Ruth O'Regan, MD||Big Ten Cancer Research Consortium|