A Study to Assess the Safety and Efficacy of the VEGFR-FGFR-PDGFR Inhibitor, Lucitanib, Given to Patients With Metastatic Breast Cancer

Phase 2

Terminated

Conditions: Estrogen Receptor Positive
Triple Negative
Metastatic Breast Cancer
HER2 Positive
HER2
Breast Cancer
MBC
ER

Interventions: Drug: Lucitanib

Registration Number: NCT02202746

Lead Sponsor: Clovis Oncology, Inc.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 178

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort A: Lucitanib (CO-3810) 10 mg daily	Lucitanib	10 mg of lucitanib daily in patients with FGFR1-amplified or 11q-amplified metastatic breast cancer.
Cohort B: Lucitanib (CO-3810) 15 mg daily	Lucitanib	15 mg of lucitanib daily in patients with FGFR1-amplified and 11q-amplified metastatic breast cancer.
Cohort C: Lucitanib (CO-3810) 10 mg daily	Lucitanib	10 mg of lucitanib daily in patients with FGFR1 non-amplified and 11q non-amplified metastatic breast cancer.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by the Investigator	From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months	The primary efficacy endpoint of PFS was calculated as 1+ the number of days from the date of first dose of study drug to disease progression or death due to any cause, whichever occurs first. Patients without a documented event of progression were censored on the date of their last adequate tumor assessment (i.e., radiologic assessment), or the date of randomization if no tumor assessments were performed. Progression events were determined by the investigator. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DR) by RECIST v1.1	From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months	DR for complete response (CR) and partial response (PR) was measured from the date that any of these best confirmed responses was first recorded until the first date that PD was objectively documented. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
Objective Response Rate (ORR) by RECIST v1.1	From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months	ORR is the percentage of patients with a best response of CR or PR according to RECIST v1.1. The best response is recorded from the start of the treatment (Day 1) until disease progression or recurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Total Score	From Cycle 1 Day 1 until end of treatment, assessed up to 29 months	FACT-B is used for assessment of health-related quality of life (QoL) in participants with breast cancer. It consists of 37 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (10 items) ranging from 0 to 40; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. FACT-B Total Score is derived from adding the five subscale scores. Total possible score ranges from 0 to 148. High scale score represents a better QoL.
Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Cmax	Study Day -7 to Study Day 1, or approximately 8 days	The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. Cmax = maximum concentration following administration of lucitanib.
Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Tmax	Study Day -7 to Study Day 1, or approximately 8 days	The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. Tmax = time to maximum concentration following administration of lucitanib
Disease Control Rate (DCR) by RECIST v1.1	From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months	The DCR is defined as the percentage of patients with a best response rate of CR, PR, or SD for at least 12 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started.
Overall Survival	Cycle 1 Day 1 to date of death, assessed up to 29 months	Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death (due to any cause). Patients without a known date of death will be censored on the date the patient was last known to be alive.
Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUClast	Study Day -7 to Study Day 1, or approximately 8 days	The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. AUClast = area under the plasma concentration time curve from time 0 to the last quantifiable time point (24 hour)
Relative Bioavailability Analysis for Tablet vs Capsule - Cmax, AUClast, AUCinf	Study Day -7 to Study Day 1, or approximately 8 days	Relative bioavailability of lucitanib was evaluated by comparison of (log-transformed) AUClast, Cmax and AUCinf of the tablet formulation to the capsule formulation using an analysis of variance (ANOVA) model with treatment as a fixed effect. The geometric means, ratio of the geometric means and 90% confidence intervals (CI) on the ratio of Tablet to Capsule (T:R) were presented for AUClast, Cmax and AUCinf. The CIs on the ratio of untransformed PK parameters were derived through reverse transformation of the 90% CI of the difference in the log scale to the 90% CI of the ratio in the original scale.
Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUCinf	Study Day -7 to Study Day 1, or approximately 8 days	The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. AUCinf = area under the plasma concentration time curve from 0 to infinity

Trial Locations

Locations (33): Arizona Oncology Associates
🇺🇸
Sedona, Arizona, United States
Moores UCSD Cancer Center
🇺🇸
La Jolla, California, United States
Cancer Care Associates Medical Group, Inc.
🇺🇸
Redondo Beach, California, United States
Central Coast Medical Oncology Group
🇺🇸
Santa Maria, California, United States
Horizon Oncology Center
🇺🇸
Lafayette, Indiana, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States
Weill Cornell Breast Center
🇺🇸
New York, New York, United States
The Center for Cancer and Blood Disorders
🇺🇸
Fort Worth, Texas, United States
Virginia Oncology Associates
🇺🇸
Norfolk, Virginia, United States
University of Southern California
🇺🇸
Los Angeles, California, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
University of Miami
🇺🇸
Deerfield Beach, Florida, United States
Memorial West Cancer Center
🇺🇸
Hollywood, Florida, United States
University of Chicago Medical Center
🇺🇸
Chicago, Illinois, United States
The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
🇺🇸
Baltimore, Maryland, United States
Vanderbilt Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸
Dallas, Texas, United States
US Oncology
🇺🇸
Houston, Texas, United States
Sarah Cannon Cancer Center
🇺🇸
Nashville, Tennessee, United States
Comprehensive Blood and Cancer Center
🇺🇸
Bakersfield, California, United States
Saint Jude Heritage Medical Center
🇺🇸
Fullerton, California, United States
Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Dana Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Comprehensive Cancer Centers of Nevada
🇺🇸
Las Vegas, Nevada, United States
Cooper University Hospital
🇺🇸
Voorhees, New Jersey, United States
University of California San Francisco
🇺🇸
San Francisco, California, United States
Northwestern University, Robert H. Lurie Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Indiana University Simon Cancer Center
🇺🇸
Indianapolis, Indiana, United States
University Hospitals Case Medical Center
🇺🇸
Cleveland, Ohio, United States
University of Pittsburgh Medical Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Sciode Medical Associates, PLLC
🇺🇸
Bronx, New York, United States
Texas Oncology - Austin Central
🇺🇸
Austin, Texas, United States
University of California, Los Angeles
🇺🇸
Los Angeles, California, United States