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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

Primary Purpose

Non-Small Cell Lung Cancer, Squamous Non-Small Cell Lung Cancer, NSCLC

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Lucitanib
Sponsored by
Clovis Oncology, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring FGFR1 amplification, FGF alteration, VEGF alteration, PDGF alteration, Tyrosine kinase inhibitor, VEGFR inhibitor, FGFR inhibitor, PDGFR inhibitor, VEGFR-FGFR inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California, Los Angeles
  • University of Colorado
  • Georgetown University
  • Emory University
  • Associates in Oncology and Hematology
  • University of Pittsburgh Medical Center
  • Tennessee Oncology
  • CHU Caen, Hôpital de la Côte de Nacre
  • CHRU Lille, Hôpital Albert Calmette
  • Hôpital Nord
  • Institut Gustave-Roussy
  • Universität Duisburg-Essen
  • Hospital Grosshansdorf
  • Pius Hospital Oldenburg
  • Ospedale San Raffaele
  • Fondazione IRCCS Istituto Nazionale Tumori
  • AOU San Luigi Gonzaga
  • Ospedale S. Maria della Misericordia
  • Hospital Universitari Vall d'Hebrón

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lucitanib

Arm Description

Lucitanib given orally once daily on a continuous schedule. Starting dose is 10 mg/day.

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR)
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.

Secondary Outcome Measures

Clinical Benefit Rate (CBR)
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
Progression-Free Survival (PFS)
Time from the date of first drug intake until the date of progression or death for any cause
Duration of response (DOR)
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
Duration of clinical benefit
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
Overall Survival (OS)
From the date of first drug intake to the date of death for any cause
Tumor growth kinetics
Will be evaluated using the following criteria: tumor size; tumor volume; tumor growth
Incidence of adverse events (AEs), clinical laboratory abnormalities, and dose modifications
PK parameters of lucitanib
Pharmacogenomic analysis of inter-patients variation in gene encoding ADME involved proteins
Pharmacodynamic (PD) evaluation of lucitanib profile
Soluble growth factors and other biomarkers, including circulating tumor DNA

Full Information

First Posted
April 7, 2014
Last Updated
July 22, 2019
Sponsor
Clovis Oncology, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02109016
Brief Title
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
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Terminated
Study Start Date
April 2014 (undefined)
Primary Completion Date
April 1, 2016 (Actual)
Study Completion Date
September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Clovis Oncology, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer, Squamous Non-Small Cell Lung Cancer, NSCLC, Small Cell Lung Cancer, SCLC, Lung Cancer, Advanced Lung Cancer, Metastatic Lung Cancer, Stage IV Lung Cancer
Keywords
FGFR1 amplification, FGF alteration, VEGF alteration, PDGF alteration, Tyrosine kinase inhibitor, VEGFR inhibitor, FGFR inhibitor, PDGFR inhibitor, VEGFR-FGFR inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lucitanib
Arm Type
Experimental
Arm Description
Lucitanib given orally once daily on a continuous schedule. Starting dose is 10 mg/day.
Intervention Type
Drug
Intervention Name(s)
Lucitanib
Intervention Description
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.
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
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.
Time Frame
Screening, every 8 weeks; up to 2 years
Secondary Outcome Measure Information:
Title
Clinical Benefit Rate (CBR)
Description
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
Time Frame
Screening, every 8 weeks; up to 2 years
Title
Progression-Free Survival (PFS)
Description
Time from the date of first drug intake until the date of progression or death for any cause
Time Frame
Screening, every 8 weeks; up to 2 years
Title
Duration of response (DOR)
Description
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
Time Frame
Screening, every 8 weeks; up to 2 years
Title
Duration of clinical benefit
Description
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
Time Frame
Screening, every 8 weeks; up to 2 years
Title
Overall Survival (OS)
Description
From the date of first drug intake to the date of death for any cause
Time Frame
Continuously; up to 2 years
Title
Tumor growth kinetics
Description
Will be evaluated using the following criteria: tumor size; tumor volume; tumor growth
Time Frame
Screening, every 8 weeks; up to 2 years
Title
Incidence of adverse events (AEs), clinical laboratory abnormalities, and dose modifications
Time Frame
Continuously; up to 2 years
Title
PK parameters of lucitanib
Time Frame
Cycle 1 Day 14 and 28, Cycle 2 Day 28, Cycle 3 Day 28
Title
Pharmacogenomic analysis of inter-patients variation in gene encoding ADME involved proteins
Time Frame
Cycle 1 Day 1
Title
Pharmacodynamic (PD) evaluation of lucitanib profile
Description
Soluble growth factors and other biomarkers, including circulating tumor DNA
Time Frame
Cycle 1 Day 1 and 14, End of Study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Georgetown University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Associates in Oncology and Hematology
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20850
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Tennessee Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
CHU Caen, Hôpital de la Côte de Nacre
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
CHRU Lille, Hôpital Albert Calmette
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Hôpital Nord
City
Marseille
ZIP/Postal Code
13915
Country
France
Facility Name
Institut Gustave-Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Universität Duisburg-Essen
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Hospital Grosshansdorf
City
Grosshansdorf
ZIP/Postal Code
22927
Country
Germany
Facility Name
Pius Hospital Oldenburg
City
Oldenburg
ZIP/Postal Code
26121
Country
Germany
Facility Name
Ospedale San Raffaele
City
Milano
ZIP/Postal Code
20132
Country
Italy
Facility Name
Fondazione IRCCS Istituto Nazionale Tumori
City
Milano
ZIP/Postal Code
20133
Country
Italy
Facility Name
AOU San Luigi Gonzaga
City
Orbassano
ZIP/Postal Code
10043
Country
Italy
Facility Name
Ospedale S. Maria della Misericordia
City
Perugia
ZIP/Postal Code
06156
Country
Italy
Facility Name
Hospital Universitari Vall d'Hebrón
City
Barcelona
State/Province
Cataluña
ZIP/Postal Code
8035
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
35844029
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.
Results Reference
derived

Learn more about this trial

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

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