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

Sponsor

Clovis Oncology, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT02109016

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

0.9

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Lucitanib	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Apr 1, 2014

Actual Primary Completion Date :

Apr 1, 2016

Actual Study Completion Date :

Sep 1, 2016

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

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
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
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
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]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Los Angeles	Los Angeles	California	United States	90095
2	University of Colorado	Aurora	Colorado	United States	80045
3	Georgetown University	Washington	District of Columbia	United States	20007
4	Emory University	Atlanta	Georgia	United States	30322
5	Associates in Oncology and Hematology	Rockville	Maryland	United States	20850
6	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15232
7	Tennessee Oncology	Nashville	Tennessee	United States	37203
8	CHU Caen, Hôpital de la Côte de Nacre	Caen		France	14033
9	CHRU Lille, Hôpital Albert Calmette	Lille		France	59037
10	Hôpital Nord	Marseille		France	13915
11	Institut Gustave-Roussy	Villejuif		France	94805
12	Universität Duisburg-Essen	Essen		Germany	45147
13	Hospital Grosshansdorf	Grosshansdorf		Germany	22927
14	Pius Hospital Oldenburg	Oldenburg		Germany	26121
15	Ospedale San Raffaele	Milano		Italy	20132
16	Fondazione IRCCS Istituto Nazionale Tumori	Milano		Italy	20133
17	AOU San Luigi Gonzaga	Orbassano		Italy	10043
18	Ospedale S. Maria della Misericordia	Perugia		Italy	06156
19	Hospital Universitari Vall d'Hebrón	Barcelona	Cataluña	Spain	8035