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

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02109016
• Other study ID #: E-3810-II-02
• Status: Terminated
• Phase: Phase 2
• Start date: April 2014
• Est. completion date: September 2016

Study information

• Verified date: July 2019
• Source: Clovis Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. completion date: September 2016
• Est. primary completion date: April 1, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 PDGFRa 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

Related Conditions & MeSH terms

• Advanced Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms
• Metastatic Lung Cancer
• Non-Small Cell Lung Cancer
• NSCLC
• SCLC
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma
• Squamous Non-Small Cell Lung Cancer
• Stage IV Lung Cancer

Intervention

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.

Locations

Country	Name	City	State
France	CHU Caen, Hôpital de la Côte de Nacre	Caen
France	CHRU Lille, Hôpital Albert Calmette	Lille
France	Hôpital Nord	Marseille
France	Institut Gustave-Roussy	Villejuif
Germany	Universität Duisburg-Essen	Essen
Germany	Hospital Grosshansdorf	Grosshansdorf
Germany	Pius Hospital Oldenburg	Oldenburg
Italy	Fondazione IRCCS Istituto Nazionale Tumori	Milano
Italy	Ospedale San Raffaele	Milano
Italy	AOU San Luigi Gonzaga	Orbassano
Italy	Ospedale S. Maria della Misericordia	Perugia
Spain	Hospital Universitari Vall d'Hebrón	Barcelona	Cataluña
United States	Emory University	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	University of California, Los Angeles	Los Angeles	California
United States	Tennessee Oncology	Nashville	Tennessee
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Associates in Oncology and Hematology	Rockville	Maryland
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Clovis Oncology, Inc.

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Spain, 

Outcome

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