Study of Ribociclib With Everolimus + Exemestane in HR+ HER2- Locally Advanced/Metastatic Breast Cancer Post Progression on CDK 4/6 Inhibitor.

Novartis Pharmaceuticals104 enrolled

Overview

The purpose of this study is determine if the triplet combination of ribociclib, everolimus and exemastane is safe and effective in the treatment of locally advanced/metastatic breast cancer following treatment with a CDK 4/6 inhibitor

This trial had two phases. The purpose of Phase I dose escalation and dose de-escalation was to determine the maximum tolerated doses (MTDs) and/or identify the recommended Phase II dose (RP2D) of the combination treatment of ribociclib+ everolimus + exemestane. The dosing was continuous in adult men and postmenopausal women with HR+ HER2-negative advanced breast cancer which was resistant to the non-steroidal aromatase inhibitors, fulvestrant or tamoxifen. The purpose of the phase II portion of this trial was to evaluate the anti-tumor activity of exemestane, everolimus and ribociclib combination therapy following progression on a CDK 4/6 inhibitor. The planned duration of the study was 30 months.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

104

Conditions

Breast Cancer

Interventions

RibociclibDRUG

supplied in 50 mg, 200 mg capsules/tablets taken orally and dosed daily for 28 day cycle

EverolimusDRUG

supplied in 2.5 mg tablets taken orally, daily for 28 day cycle

ExemestaneDRUG

supplied in 25 mg tablets taken orally, daily for 28 day cycle

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adult men and women * Patient has a confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory and has HER2-negative breast cancer * Patient must have either measurable disease by RECIST 1.1 or bone lesions in absence of measurable disease. * ECOG Performance Status 0 - 1 * Disease refractory to either, AI, tamoxifen or fulvestrant * Previously treated on any CDK 4/6 inhibitor. * Patient has adequate bone marrow and organ function. Exclusion Criteria: * Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment. * Patient has received more than one line of chemotherapy for advanced disease. * Previous treatment with mTOR inhibitors, or exemestane for advanced disease. * Progressed on more than one CDK 4/6 inhibitor * Patient with CNS involvement unless they are at least 4 weeks from prior therapy completion. * Clinically significant, uncontrolled heart disease and/or recent cardiac events.

Locations (25)

Outcomes

Primary Outcomes

Participants With Dose Limiting Toxicities by Preferred Term in Cycle 1 (28 Days) - in Phase I

A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a reasonably possible relationship to the study medication(s) and is unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 28 days of treatment (cycle 1) and meets any of the criteria defined in the protocol. National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 4.03 will be used for all grading.

Time frame: Baseline up to 28 days

Clinical Benefit Rate as Per Central Review by Group- Phase II

Clinical Benefit Rate (CBR) is defined as the percentage of participants with a complete response (CR) or partial response (PR) or with stable disease (SD) as per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 or Non-Complete Response or Non-Progressive Disease (NCRNPD) during first 24 weeks of first dose. CR=disappearance of all non-nodal target lesions, PR=at least a 30% decrease in the sum of diameter of all target lesions, SD=neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD), PD=at least a 20% increase in the sum of diameter of all target lesions. The hypothesis was to be rejected if the lower limit of the 95% Confidence Interval for Clinical Benefit Rate (CBR) was greater than 10%.

Time frame: From baseline up to 24 weeks

Best Overall Responses (BOR) Summary Table as Per Central Review by Group - Phase II

Complete response (CR) or partial response (PR), or stable disease (SD) at 24 weeks as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Non-CR Non-PD (NCRNPD) at Week 24.

Time frame: Baseline up to 24 weeks and at 24 weeks

Secondary Outcomes

Everolimus Pharmacokinetic Plasma Concentrations by Cohort - Phase I

Plasma concentrations; below limit of quantitation values set to zero

Data from ClinicalTrials.gov

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