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

June 20, 2020 updated by: Clovis Oncology, Inc.

A Phase 2, Open-label, Multicenter, Safety and Efficacy Study of Oral Lucitanib in Patients With FGF Aberrant Metastatic Breast Cancer

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

178

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Sedona, Arizona, United States, 86336
        • Arizona Oncology Associates
    • California
      • Bakersfield, California, United States, 93309
        • Comprehensive Blood and Cancer Center
      • Fullerton, California, United States, 92835
        • Saint Jude Heritage Medical Center
      • La Jolla, California, United States, 92093
        • Moores UCSD Cancer Center
      • Los Angeles, California, United States, 90033
        • University of Southern California
      • Los Angeles, California, United States, 90095
        • University of California, Los Angeles
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
      • Redondo Beach, California, United States, 90277
        • Cancer Care Associates Medical Group, Inc.
      • San Francisco, California, United States, 94115
        • University of California San Francisco
      • Santa Maria, California, United States, 93454
        • Central Coast Medical Oncology Group
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Yale University
    • Florida
      • Deerfield Beach, Florida, United States, 33442
        • University of Miami
      • Hollywood, Florida, United States, 33021
        • Memorial West Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
      • Chicago, Illinois, United States, 60611
        • Northwestern University, Robert H. Lurie Comprehensive Cancer Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Simon Cancer Center
      • Lafayette, Indiana, United States, 47905
        • Horizon Oncology Center
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada
    • New Jersey
      • Voorhees, New Jersey, United States, 08043
        • Cooper University Hospital
    • New York
      • Bronx, New York, United States, 10469
        • Sciode Medical Associates, PLLC
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10065
        • Weill Cornell Breast Center
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Case Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Cancer Center
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Ingram Cancer Center
    • Texas
      • Austin, Texas, United States, 78731
        • Texas Oncology - Austin Central
      • Dallas, Texas, United States, 75246
        • Texas Oncology - Baylor Charles A. Sammons Cancer Center
      • Fort Worth, Texas, United States, 76104
        • The Center for Cancer and Blood Disorders
      • Houston, Texas, United States, 77024
        • US Oncology
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • Virginia Oncology Associates

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort A: Lucitanib (CO-3810) 10 mg daily
10 mg of lucitanib daily in patients with FGFR1-amplified or 11q-amplified metastatic breast cancer.
Drug: Lucitanib
Lucitanib is a potent, orally available selective inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors (FGFR1-3), vascular endothelial growth factor receptors (VEGFR1-3), and platelet-derived growth factor receptors alpha and beta (PDGFR alpha and beta)
Other Names:
  • CO-3810
Experimental: Cohort B: Lucitanib (CO-3810) 15 mg daily
15 mg of lucitanib daily in patients with FGFR1-amplified and 11q-amplified metastatic breast cancer.
Drug: Lucitanib
Lucitanib is a potent, orally available selective inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors (FGFR1-3), vascular endothelial growth factor receptors (VEGFR1-3), and platelet-derived growth factor receptors alpha and beta (PDGFR alpha and beta)
Other Names:
  • CO-3810
Experimental: Cohort C: Lucitanib (CO-3810) 10 mg daily
10 mg of lucitanib daily in patients with FGFR1 non-amplified and 11q non-amplified metastatic breast cancer.
Drug: Lucitanib
Lucitanib is a potent, orally available selective inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors (FGFR1-3), vascular endothelial growth factor receptors (VEGFR1-3), and platelet-derived growth factor receptors alpha and beta (PDGFR alpha and beta)
Other Names:
  • CO-3810

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by the Investigator
Time Frame: 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.
From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) by RECIST v1.1
Time Frame: 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.
From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months
Duration of Response (DR) by RECIST v1.1
Time Frame: 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.
From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months
Disease Control Rate (DCR) by RECIST v1.1
Time Frame: 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.
From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months
Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Cmax
Time Frame: 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.
Study Day -7 to Study Day 1, or approximately 8 days
Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Tmax
Time Frame: 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
Study Day -7 to Study Day 1, or approximately 8 days
Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUClast
Time Frame: 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)
Study Day -7 to Study Day 1, or approximately 8 days
Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUCinf
Time Frame: 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
Study Day -7 to Study Day 1, or approximately 8 days
Relative Bioavailability Analysis for Tablet vs Capsule - Cmax, AUClast, AUCinf
Time Frame: 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.
Study Day -7 to Study Day 1, or approximately 8 days
Overall Survival
Time Frame: 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.
Cycle 1 Day 1 to date of death, assessed up to 29 months
Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Total Score
Time Frame: 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.
From Cycle 1 Day 1 until end of treatment, assessed up to 29 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Clovis Oncology, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 9, 2014

Primary Completion (Actual)

January 17, 2017

Study Completion (Actual)

January 18, 2017

Study Registration Dates

First Submitted

July 25, 2014

First Submitted That Met QC Criteria

July 25, 2014

First Posted (Estimate)

July 29, 2014

Study Record Updates

Last Update Posted (Actual)

June 23, 2020

Last Update Submitted That Met QC Criteria

June 20, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CO-3810-025

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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