An Open-Label, Phase Ib/II Clinical Trial Of Cdk 4/6 Inhibitor, Ribociclib (Lee011), In Combination With Trastuzumab Or T-Dm1 For Advanced/Metastatic Her2-Positive Breast Cancer.

Completed · Phase 1/Phase 2

Conditions studied: Breast Cancer

In brief

Participants that have breast cancer that has spread to other parts of the body, is positive for a protein called HER2, and has not responded to standard treatment. This research study is a way of gaining new knowledge about the combination of Ribociclib with other drugs as a possible treatment for this diagnosis.

Key facts

Study ID

NCT02657343

Run by

Dana-Farber Cancer Institute

People needed

25

Starts

2016-03-09

Expected to finish

2022-06-30

Last updated by the study team

2022-08-01

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants must have histologically confirmed invasive breast cancer, with locally advanced or metastatic disease. Patients without pathologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation.
• The primary tumor, and/or metastasis must have been tested for ER, PR and HER 2, and be HER2 positive as defined by the 2013 ASCO-CAP guidelines.
• Measureable disease by RECIST 1.1 (at least one lesion that can be accurately measured in at least one dimension > 20mm with conventional imaging techniques or > 10mm with spiral CT or MRI) or evaluable disease. Bone lesions (blastic, lytic, or mixed) in the absence of measurable disease as defined above are also acceptable.
• Prior treatment
• Cohort A:
• Prior treatment with at least one regimen containing Trastuzumab and taxane.
• No prior treatment with T-DM1 that was discontinued due to disease progression or toxicity.
• No more than 4 prior lines of therapy in the metastatic setting.
• Cohort B:
• Must have received prior Trastuzumab, pertuzumab, and T-DM1 in neo-adjuvant, adjuvant, or metastatic setting.
• No limit on prior lines of therapies.
• Cohort C:
• Must have received prior Trastuzumab, pertuzumab, and T-DM1 in neo=adjuvant, adjuvant, or metastatic setting.
• Maximum of 5 prior lines of therapy for metastatic disease.
• Prior treatment with fulvestrant is permitted.
• Age ≥ 18 years.
• ECOG performance status 0-2 (see Appendix A)
• Participants must have adequate organ and bone marrow function as defined below:
• Absolute neutrophil count ≥1.5 x 109/L
• Platelets ≥100 x 109/L
• Hemoglobin ≥ 9 g/dL
• Total bilirubin < 1.5xULN; or total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN in patients with well-documented Gilbert's Syndrome.
• Serum creatinine ≤ 1.5 mg/dL or calculated GFR ≥ 50mL/min
• ALT/AST <2.5x ULN; if liver metastases, ALT/AST ≤5.0x ULN
• INR ≤ 1.5

You may not qualify if…

• Participants who have had chemotherapy within 14 days prior registration or those who have not recovered from all toxicities related to prior anticancer therapies to NCI-CTCAE version 4.03 Grade ≤1 (Exception to this criterion: patients with any grade of alopecia are allowed to enter the study). There is no washout period required for Trastuzumab.
• Participants who have received radiotherapy ≤ 2 weeks prior to starting study drug, and who have not recovered to grade 1 or better from related side effects of such therapy (except alopecia and neuropathy) and/or in whom ≥ 25% of the bone marrow was irradiated.
• Participants who have previously received a CDK 4/6 inhibitor.
• Participants with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
• At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
• Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ribociclib, T-DM1 (Cohort A) and/or Trastuzumab (Cohort B).
• In general, the use of any concomitant medication deemed necessary for the care of the patient is permitted in this study, except as specifically prohibited below. Combination administration of study drugs could result in drug-drug interactions (DDI) that could potentially lead to reduced activity or enhanced toxicity of the concomitant medication and/or Ribociclib.
• Patient is currently receiving any of the following medications and cannot discontinue use within 7 days prior to starting study drug (see (Tables 1 and 2, Appendix B for details):
• Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges
• That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
• Herbal preparations/medications, dietary supplements.
• The list provided here (and in Tables 1 and 2, Appendix B) is not comprehensive and is only meant to be used as a guide. The list is based on the Oncology Clinical Pharmacology Drug-Drug Interaction Database (release date: 29 Oct 2012), which was compiled from the Indiana University School of Medicine's P450 Drug Interaction Table.
• http://medicine.iupui.edu/clinpharm/ddis/main-table/) and supplemented with the FDA Draft Guidance for Industry, Drug Interaction Studies - Study Design, Data Analysis, and Implications for Dosing and Labeling (February 2012) (http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm292362.pdf), and the University of Washington's Drug Interaction Database (http://www.druginteractioninfo.org/). For current lists of medications that may cause QT prolongation and/or torsades de pointes (TdP), refer to the CredibleMeds® website (https://crediblemeds.org/).
• Participants who have any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.).
• Participants who have had major surgery within 2 weeks prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery).
• Participants who have clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities including any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening
• History of documented congestive heart failure (New York Heart Association functional classification III-IV)
• Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block
• Documented cardiomyopathy
• Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening
• Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following
• Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
• Inability to determine the QT interval on screening (QTcF, using Fridericia's correction)

Where it is running

• Massacusetts General Hospital — Boston, Massachusetts, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States

Full record on ClinicalTrials.gov

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