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

Phase 2

Terminated

• Conditions: Squamous Non-Small Cell Lung Cancer; SCLC; NSCLC; Non-Small Cell Lung Cancer; Small Cell Lung Cancer; Advanced Lung Cancer; Stage IV Lung Cancer; Lung Cancer; Metastatic Lung Cancer
• Interventions: Drug: Lucitanib

• Registration Number: NCT02109016
• 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 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.

Study Timeline

• Study Start: 2014-04
• Study First Submitted: 2014-04-07
• Study First Submitted QC: 2014-04-07
• Study First Posted: 2014-04-09
• Primary Completion: 2016-04-01
• Study Completion: 2016-09
• Disposition First Submitted: 2017-07-21
• Disposition First Submitted QC: 2017-07-21
• Disposition First Posted: 2017-07-24
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-22
• Last Update Posted: 2019-07-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 18

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	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.

Secondary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	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
Clinical Benefit Rate (CBR)	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
Tumor growth kinetics	Screening, every 8 weeks; up to 2 years	Will be evaluated using the following criteria: tumor size; tumor volume; tumor growth
Incidence of adverse events (AEs), clinical laboratory abnormalities, and dose modifications	Continuously; up to 2 years
PK parameters of lucitanib	Cycle 1 Day 14 and 28, Cycle 2 Day 28, Cycle 3 Day 28
Duration of response (DOR)	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
Duration of clinical benefit	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
Overall Survival (OS)	Continuously; up to 2 years	From the date of first drug intake to the date of death for any cause
Pharmacogenomic analysis of inter-patients variation in gene encoding ADME involved proteins	Cycle 1 Day 1
Pharmacodynamic (PD) evaluation of lucitanib profile	Cycle 1 Day 1 and 14, End of Study	Soluble growth factors and other biomarkers, including circulating tumor DNA

Trial Locations

Locations (19)

Emory University; 🇺🇸 Atlanta, Georgia, United States

Associates in Oncology and Hematology; 🇺🇸 Rockville, Maryland, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Hôpital Nord; 🇫🇷 Marseille, France

Institut Gustave-Roussy; 🇫🇷 Villejuif, France

Universität Duisburg-Essen; 🇩🇪 Essen, Germany

CHU Caen, Hôpital de la Côte de Nacre; 🇫🇷 Caen, France

CHRU Lille, Hôpital Albert Calmette; 🇫🇷 Lille, France

Hospital Grosshansdorf; 🇩🇪 Grosshansdorf, Germany

Pius Hospital Oldenburg; 🇩🇪 Oldenburg, Germany

Ospedale San Raffaele; 🇮🇹 Milano, Italy

AOU San Luigi Gonzaga; 🇮🇹 Orbassano, Italy

Ospedale S. Maria della Misericordia; 🇮🇹 Perugia, Italy

Hospital Universitari Vall d'Hebrón; 🇪🇸 Barcelona, Cataluña, Spain

University of Colorado; 🇺🇸 Aurora, Colorado, United States

University of California, Los Angeles; 🇺🇸 Los Angeles, California, United States

Fondazione IRCCS Istituto Nazionale Tumori; 🇮🇹 Milano, Italy

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

Georgetown University; 🇺🇸 Washington, District of Columbia, United States