Clinical trial NCT02109016: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: Clovis Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2014-04-09
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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 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.

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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Screening, every 8 weeks; up to 2 years
Secondary outcomes:
measure: Clinical Benefit Rate (CBR)
timeFrame: Screening, every 8 weeks; up to 2 years
measure: Progression-Free Survival (PFS)
timeFrame: Screening, every 8 weeks; up to 2 years
measure: Duration of response (DOR)
timeFrame: Screening, every 8 weeks; up to 2 years
measure: Duration of clinical benefit
timeFrame: Screening, every 8 weeks; up to 2 years
measure: Overall Survival (OS)
timeFrame: Continuously; up to 2 years
measure: Tumor growth kinetics
timeFrame: Screening, every 8 weeks; up to 2 years
measure: Incidence of adverse events (AEs), clinical laboratory abnormalities, and dose modifications
timeFrame: Continuously; up to 2 years
measure: PK parameters of lucitanib
timeFrame: Cycle 1 Day 14 and 28, Cycle 2 Day 28, Cycle 3 Day 28
measure: Pharmacogenomic analysis of inter-patients variation in gene encoding ADME involved proteins
timeFrame: Cycle 1 Day 1
measure: Pharmacodynamic (PD) evaluation of lucitanib profile
timeFrame: Cycle 1 Day 1 and 14, End of Study
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Rockville
country: United States
facility: Associates in Oncology and Hematology
state: Maryland
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Caen
country: France
facility: CHU Caen, Hôpital de la Côte de Nacre
city: Lille
country: France
facility: CHRU Lille, Hôpital Albert Calmette
city: Marseille
country: France
facility: Hôpital Nord
city: Villejuif
country: France
facility: Institut Gustave-Roussy
city: Essen
country: Germany
facility: Universität Duisburg-Essen
city: Grosshansdorf
country: Germany
facility: Hospital Grosshansdorf
city: Oldenburg
country: Germany
facility: Pius Hospital Oldenburg
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale Tumori
city: Orbassano
country: Italy
facility: AOU San Luigi Gonzaga
city: Perugia
country: Italy
facility: Ospedale S. Maria della Misericordia
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
state: Cataluña
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.