A Study to Assess the Efficacy and Safety of the VEGFR-FGFR Inhibitor, Lucitanib, Given to Patients With Advanced/Metastatic Lung Cancer and FGF, VEGF, or PDGF Related Genetic Alterations

July 22, 2019 updated by: Clovis Oncology, Inc.

A Single Arm, Open-label, Phase 2 Study to Assess the Efficacy and Safety of Lucitanib Given Orally as a Single Agent to Patients With Advanced/Metastatic Lung Cancer and FGF, VEGF, or PDGF Related Genetic Alterations

The purpose of this study is to determine whether lucitanib is safe and effective in the treatment of patients with advanced/metastatic lung cancer and fibroblast growth factor (FGF), vascular endothelial growth factor receptor (VEGF), or platelet derived growth factor (PDGF) related genetic alterations.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Lucitanib is an oral inhibitor of the tyrosine kinase activity of FGFR 1-3, VEGFR 1-3, and PDGFR α/β. Lucitanib has demonstrated potent anti-tumor and anti-angiogenic activity in vitro proliferation assays and in vivo using human tumor xenograft models, with a trend for stronger efficacy in those with genomic aberrancies of FGF or PDGF. Abnormalities in the FGF, VEGF, and PDGF-related genes are observed across lung cancer histologies.

The first in human trial of lucitanib demonstrated that daily lucitanib is clinically active in patients with advanced solid tumors. Specifically, patients with FGFR1-amplification appeared to derive particular benefit from lucitanib.

Based on these results, this study is designed to explore the safety and anti-tumor activity of daily lucitanib in lung cancer patients with FGF, VEGF, and PDGF genetic alterations.

Study Type

Interventional

Enrollment (Actual)

18

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

  • France
      • Caen, France, 14033
        • CHU Caen, Hôpital de la Côte de Nacre
      • Lille, France, 59037
        • CHRU Lille, Hôpital Albert Calmette
      • Marseille, France, 13915
        • Hopital Nord
      • Villejuif, France, 94805
        • Institut Gustave-Roussy
  • Germany
      • Essen, Germany, 45147
        • Universität Duisburg-Essen
      • Grosshansdorf, Germany, 22927
        • Hospital Grosshansdorf
      • Oldenburg, Germany, 26121
        • Pius Hospital Oldenburg
  • Italy
      • Milano, Italy, 20132
        • Ospedale San Raffaele
      • Milano, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale Tumori
      • Orbassano, Italy, 10043
        • AOU San Luigi Gonzaga
      • Perugia, Italy, 06156
        • Ospedale S. Maria Della Misericordia
  • Spain
    • Cataluña
      • Barcelona, Cataluña, Spain, 8035
        • Hospital Universitari Vall d'Hebron
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • University of California, Los Angeles
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Maryland
      • Rockville, Maryland, United States, 20850
        • Associates in Oncology and Hematology
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology

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 advanced/metastatic SCLC or NSCLC
  • Any of the following tumor tissue based genetic alterations: FGFR1, FGFR2, FGFR3, VEGFA, or PDGFRα amplification; Any FGFR1, FGFR2, or FGFR3 gene fusion; FGFR1, FGFR2, or FGFR3 activating mutation
  • Availability of tumor tissue sample suitable for the central confirmation of the genetic alteration and exploratory analyses
  • Eastern Cooperative Oncology Group (ECOG) of 0 or 1
  • Measurable disease per RECIST 1.1
  • Documented radiographic disease progression following at least one line of therapy in the advanced/metastatic setting

Exclusion Criteria:

  • Tumors that are invading a major vessel; NSCLC tumors abutting to a major vessel
  • Uncontrolled hypertension, defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg with optimized anti-hypertensive therapy
  • Uncontrolled hypothyroidism defined as serum thyroid stimulating hormone (TSH) higher than 5 mIU/mL while receiving appropriate thyroid hormone therapy
  • Symptomatic and/or untreated central nervous system metastases
  • Presence of another active cancer
  • Ongoing adverse events from surgery or prior anti-cancer therapies, including radiation, targeted, or cytotoxic therapies
  • Pregnant or breastfeeding women

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lucitanib
Lucitanib given orally once daily on a continuous schedule. Starting dose is 10 mg/day.
Drug: Lucitanib

Lucitanib given orally to all patients, once daily (q.d.), on a continuous schedule over 28-day cycles, in fasting conditions (at least 2 hours prior to and 2 hours after any meal), until progressive disease or unacceptable toxicity.

Starting dose is 10 mg/day and can be reduced in 2.5 mg decrements to 5 mg/day based on individual tolerability.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Screening, every 8 weeks; up to 2 years
Proportion of patients in whom a confirmed Complete Response (CR) or a confirmed Partial Response (PR), as best overall response according to RECIST criteria, is observed.
Screening, every 8 weeks; up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Benefit Rate (CBR)
Time Frame: Screening, every 8 weeks; up to 2 years
Proportion of patients in whom a confirmed CR or confirmed PR or a prolonged Stable Disease (SD) (≥ 6 months), as best overall response according to RECIST, is observed
Screening, every 8 weeks; up to 2 years
Progression-Free Survival (PFS)
Time Frame: Screening, every 8 weeks; up to 2 years
Time from the date of first drug intake until the date of progression or death for any cause
Screening, every 8 weeks; up to 2 years
Duration of response (DOR)
Time Frame: Screening, every 8 weeks; up to 2 years
For responders (i.e. patients with best overall response CR or PR), the interval from the time of first documentation of response to the date of progression or death for any cause
Screening, every 8 weeks; up to 2 years
Duration of clinical benefit
Time Frame: Screening, every 8 weeks; up to 2 years
For responders and patients with SD as best overall response, time from the first drug intake until the date of progression or death for any cause
Screening, every 8 weeks; up to 2 years
Overall Survival (OS)
Time Frame: Continuously; up to 2 years
From the date of first drug intake to the date of death for any cause
Continuously; up to 2 years
Tumor growth kinetics
Time Frame: Screening, every 8 weeks; up to 2 years
Will be evaluated using the following criteria: tumor size; tumor volume; tumor growth
Screening, every 8 weeks; up to 2 years
Incidence of adverse events (AEs), clinical laboratory abnormalities, and dose modifications
Time Frame: Continuously; up to 2 years
Continuously; up to 2 years
PK parameters of lucitanib
Time Frame: Cycle 1 Day 14 and 28, Cycle 2 Day 28, Cycle 3 Day 28
Cycle 1 Day 14 and 28, Cycle 2 Day 28, Cycle 3 Day 28
Pharmacogenomic analysis of inter-patients variation in gene encoding ADME involved proteins
Time Frame: Cycle 1 Day 1
Cycle 1 Day 1
Pharmacodynamic (PD) evaluation of lucitanib profile
Time Frame: Cycle 1 Day 1 and 14, End of Study
Soluble growth factors and other biomarkers, including circulating tumor DNA
Cycle 1 Day 1 and 14, End of Study

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

April 1, 2014

Primary Completion (Actual)

April 1, 2016

Study Completion (Actual)

September 1, 2016

Study Registration Dates

First Submitted

April 7, 2014

First Submitted That Met QC Criteria

April 7, 2014

First Posted (Estimate)

April 9, 2014

Study Record Updates

Last Update Posted (Actual)

July 29, 2019

Last Update Submitted That Met QC Criteria

July 22, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • E-3810-II-02

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.

Clinical Trials on Small Cell Lung Cancer

Clinical Trials on Lucitanib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mozambique

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe