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

NCT ID: NCT02732119

Last Updated: 2021-05-05

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

104 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-06-14

Study Completion Date

2020-02-25

Brief Summary

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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

Detailed Description

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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.

Conditions

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Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort A

Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B

Group Type EXPERIMENTAL

Ribociclib

Intervention Type DRUG

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

Everolimus

Intervention Type DRUG

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

Exemestane

Intervention Type DRUG

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

Cohort B

Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally

Group Type EXPERIMENTAL

Ribociclib

Intervention Type DRUG

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

Everolimus

Intervention Type DRUG

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

Exemestane

Intervention Type DRUG

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

Cohort C

Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally

Group Type EXPERIMENTAL

Ribociclib

Intervention Type DRUG

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

Everolimus

Intervention Type DRUG

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

Exemestane

Intervention Type DRUG

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

Group 1

Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally

Group Type EXPERIMENTAL

Ribociclib

Intervention Type DRUG

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

Everolimus

Intervention Type DRUG

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

Exemestane

Intervention Type DRUG

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

Group 2

Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally

Group Type EXPERIMENTAL

Ribociclib

Intervention Type DRUG

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

Everolimus

Intervention Type DRUG

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

Exemestane

Intervention Type DRUG

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

Interventions

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Ribociclib

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

Intervention Type DRUG

Everolimus

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

Intervention Type DRUG

Exemestane

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Ironwood Cancer and Research Centers Ironwood Cancer

Chandler, Arizona, United States

Site Status

Highlands Oncology Group

Fayetteville, Arkansas, United States

Site Status

UCLA Department of Medicine UCLA Hematology/Oncology

Los Angeles, California, United States

Site Status

University of California San Francisco Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Central Coast Medical Oncology Corporation Onc Dept

Santa Maria, California, United States

Site Status

Yale University School of Medicine Smilow Cancer Hospital

New Haven, Connecticut, United States

Site Status

Florida Cancer Research Institute Dept of Oncology

Davie, Florida, United States

Site Status

Florida Cancer Specialists FL Cancer Specialists

Fort Myers, Florida, United States

Site Status

UF Health Cancer Center at Orlando Health UF Health (4)

Orlando, Florida, United States

Site Status

Florida Cancer Specialists-North

St. Petersburg, Florida, United States

Site Status

Atlanta Cancer Center

Atlanta, Georgia, United States

Site Status

University of Kansas Cancer Center Univ of KS CC Medical Pavilion

Westwood, Kansas, United States

Site Status

Massachusetts General Hospital Mass Gen Hos Cancer Center

Boston, Massachusetts, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

St. Luke's Cancer Institute Regulatory

Kansas City, Missouri, United States

Site Status

Research Medical Center HCA Midwest Division

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine Washington U School of Medicin

St Louis, Missouri, United States

Site Status

Saint Barnabas Medical Center

Livingston, New Jersey, United States

Site Status

Penn State Hershey Cancer Institute

Hershey, Pennsylvania, United States

Site Status

University of Pennsylvania Medical Center Abramson Cancer Ctr of the Uni

Philadelphia, Pennsylvania, United States

Site Status

Sarah Cannon Research Institute Sarah Cannon Research Insti

Nashville, Tennessee, United States

Site Status

Oncology Consultants Oncology Consultants

Houston, Texas, United States

Site Status

MD Anderson Cancer Center/University of Texas MDACC

Houston, Texas, United States

Site Status

Huntsman Cancer Institute Huntsman Cancer Insti

Salt Lake City, Utah, United States

Site Status

Northwest Medical Specialties Dept of Onc

Tacoma, Washington, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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CLEE011XUS29

Identifier Type: -

Identifier Source: org_study_id

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