Clinical trial NCT02732119: Study of Ribociclib With Everolimus + Exemestane in HR+ HER2- Locally Advanced/Metastatic Breast Cancer Post Progression on CDK 4/6 Inhibitor.
Official title: A Phase I/II, Single Arm, Open-label Study of Ribociclib in Combination With Everolimus + Exemestane in the Treatment of Men and Postmenopausal Women With HR+, HER2- Locally Advanced or Metastatic Breast Cancer Following Progression on a CDK 4/6 Inhibitor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: HR-positive
HER2-negative
Advanced breast cancer
LEE011
ribociclib
everolimus
Afinitor
exemestane
Aromasin
CDK
CDK4
CDK6
CDK4/6
CDK4/6 inhibitor
Phase I
Phase II
ER-positive
PR-positive
Postmenopausal
adult
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-04-08
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Participants With Dose Limiting Toxicities by Preferred Term in Cycle 1 (28 Days) - in Phase I
timeFrame: Baseline up to 28 days
measure: Clinical Benefit Rate as Per Central Review by Group- Phase II
timeFrame: From baseline up to 24 weeks
measure: Best Overall Responses (BOR) Summary Table as Per Central Review by Group - Phase II
timeFrame: Baseline up to 24 weeks and at 24 weeks
Secondary outcomes:
measure: Everolimus Pharmacokinetic Plasma Concentrations by Cohort - Phase I
timeFrame: Cycle 1,2: Day 1 and 15 - pre-dose, 2 and 4 hour post dose, Cycle 3 , Day 1 - pre-dose
measure: Best Overall Responses (BOR) Summary Table as Per Central Review by Cohort - Phase I
timeFrame: From baseline up to 24 weeks
measure: Clinical Benefit Rate as Per Central Review by Dose Cohort - Phase I
timeFrame: Baseline up to 24 weeks and at week 24
measure: Summary of Progression-free Survival (PFS) (Months), as Per Central Review by Group - Phase II
timeFrame: Baseline up to approximately 32 months
measure: Overall Survival (OS) by Group - Phase II
timeFrame: Baseline up to approximately 32 months
measure: Duration of Overall Response (DOR) by Group - Phase II
timeFrame: Baseline up to approximately 16 months
measure: Time to Definitive Deterioration of ECOG Performance Status in One Category of the Score by Group - Phase II
timeFrame: Baseline up to approximately 8 months
measure: Everolimus Pharmacokinetic Plasma Concentrations - Phase II
timeFrame: Cycle 1,2: Day 1 and 15 - pre-dose, 2 and 4 hour post dose, Cycle 3 , Day 1 - pre-dose
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer and Research Centers Ironwood Cancer
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Los Angeles
country: United States
facility: UCLA Department of Medicine UCLA Hematology/Oncology
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Comprehensive Cancer Center
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation Onc Dept
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine Smilow Cancer Hospital
state: Connecticut
city: Davie
country: United States
facility: Florida Cancer Research Institute Dept of Oncology
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists FL Cancer Specialists
state: Florida
city: Orlando
country: United States
facility: UF Health Cancer Center at Orlando Health UF Health (4)
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists-North
state: Florida
city: Atlanta
country: United States
facility: Atlanta Cancer Center
state: Georgia
city: Westwood
country: United States
facility: University of Kansas Cancer Center Univ of KS CC Medical Pavilion
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital Mass Gen Hos Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Kansas City
country: United States
facility: St. Luke's Cancer Institute Regulatory
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center HCA Midwest Division
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine Washington U School of Medicin
state: Missouri
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Hershey
country: United States
facility: Penn State Hershey Cancer Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Medical Center Abramson Cancer Ctr of the Uni
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute Sarah Cannon Research Insti
state: Tennessee
city: Houston
country: United States
facility: Oncology Consultants Oncology Consultants
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center/University of Texas MDACC
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute Huntsman Cancer Insti
state: Utah
city: Tacoma
country: United States
facility: Northwest Medical Specialties Dept of Onc
state: Washington
Study officials:
References: