Clinical trial NCT02202746: A Study to Assess the Safety and Efficacy of the VEGFR-FGFR-PDGFR Inhibitor, Lucitanib, Given to Patients With Metastatic Breast Cancer
Official title: A Phase 2, Open-label, Multicenter, Safety and Efficacy Study of Oral Lucitanib in Patients With FGF Aberrant Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Metastatic Breast Cancer
MBC
HER2 Positive
HER2
Estrogen Receptor Positive
ER
Triple Negative
Keywords: Breast cancer
Metastatic breast cancer
MBC
HER2 positive
HER2+
Estrogen receptor positive
ER+
Triple negative
FGFR1
11q
FGF aberrant
Biomarker negative
FGF non-aberrant
Lead sponsor: Clovis Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2014-07-29
Enrollment: 178
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether lucitanib is safe and effective in the treatment of patients with FGF aberrant metastatic breast cancer, as well as in the treatment of patients with biomarker negative (FGF non-aberrant) metastatic breast cancer.

Detailed description: Lucitanib is a selective, orally available tyrosine kinase inhibitor targeting FGFR1-3, VEGFR1-3, and PDGFRα and β, with activity in relevant cell lines and animal models.

The first in human trial of lucitanib demonstrated that daily dosing with lucitanib can provide durable clinical responses in patients with FGFR1- or 11q (FGF3, FGF4, Cyclin D1, or FGF19)-amplified breast cancer. RECIST partial responses (PRs) were also observed in patients not known to have FGF abnormalities.

Based on these results, this study is designed to explore the safety and anti-tumor activity of daily lucitanib in breast cancer patients with and without alterations of the FGF pathway.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed metastatic breast cancer relapsed or refractory to approved standard available treatment
* Prior treatment with standard first line therapy in the metastatic setting
* Availability of tumor tissue sufficient for confirmatory testing of FGFR1 and 11q amplification status
* Demonstrated progression of disease by radiological or clinical assessment (Measurable disease according to RECIST Version 1.1 is NOT required for enrollment)
* Estimated life expectancy \>6 months

Exclusion Criteria:

* Current or recent treatment with biologic anticancer therapies
* Ongoing AEs from prior anticancer therapies
* Active central nervous system (CNS) metastases
* Clinically significant or uncontrolled hypertension or cardiac disease
* Females who are pregnant or breastfeeding

Primary outcomes:
measure: Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by the Investigator
timeFrame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months
Secondary outcomes:
measure: Objective Response Rate (ORR) by RECIST v1.1
timeFrame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months
measure: Duration of Response (DR) by RECIST v1.1
timeFrame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months
measure: Disease Control Rate (DCR) by RECIST v1.1
timeFrame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months
measure: Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Cmax
timeFrame: Study Day -7 to Study Day 1, or approximately 8 days
measure: Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Tmax
timeFrame: Study Day -7 to Study Day 1, or approximately 8 days
measure: Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUClast
timeFrame: Study Day -7 to Study Day 1, or approximately 8 days
measure: Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUCinf
timeFrame: Study Day -7 to Study Day 1, or approximately 8 days
measure: Relative Bioavailability Analysis for Tablet vs Capsule - Cmax, AUClast, AUCinf
timeFrame: Study Day -7 to Study Day 1, or approximately 8 days
measure: Overall Survival
timeFrame: Cycle 1 Day 1 to date of death, assessed up to 29 months
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Total Score
timeFrame: From Cycle 1 Day 1 until end of treatment, assessed up to 29 months
Other outcomes:
Locations:
city: Sedona
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Fullerton
country: United States
facility: Saint Jude Heritage Medical Center
state: California
city: La Jolla
country: United States
facility: Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Redondo Beach
country: United States
facility: Cancer Care Associates Medical Group, Inc.
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Group
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Deerfield Beach
country: United States
facility: University of Miami
state: Florida
city: Hollywood
country: United States
facility: Memorial West Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University, Robert H. Lurie Comprehensive Cancer Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Lafayette
country: United States
facility: Horizon Oncology Center
state: Indiana
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Voorhees
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Bronx
country: United States
facility: Sciode Medical Associates, PLLC
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Breast Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Austin Central
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: The Center for Cancer and Blood Disorders
state: Texas
city: Houston
country: United States
facility: US Oncology
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
Study officials:
References:
citation: Liao M, Zhou J, Wride K, Lepley D, Cameron T, Sale M, Xiao J. Population Pharmacokinetic Modeling of Lucitanib in Patients with Advanced Cancer. Eur J Drug Metab Pharmacokinet. 2022 Sep;47(5):711-723. doi: 10.1007/s13318-022-00773-w. Epub 2022 Jul 18.