Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
E-3810-II-02
- NCT ID:
NCT02109016
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
Interventions
| Drug | Synonyms | Arms |
|---|
| Lucitanib | | Lucitanib |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Lucitanib | Experimental | Lucitanib given orally once daily on a continuous schedule. Starting dose is 10 mg/day. | |
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Objective Response Rate (ORR) |
| Time Frame: | Screening, every 8 weeks; up to 2 years |
| Safety Issue: | |
| 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. |
Secondary Outcome Measures
| Measure: | Clinical Benefit Rate (CBR) |
| Time Frame: | Screening, every 8 weeks; up to 2 years |
| Safety Issue: | |
| 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 |
| Measure: | Progression-Free Survival (PFS) |
| Time Frame: | Screening, every 8 weeks; up to 2 years |
| Safety Issue: | |
| Description: | Time from the date of first drug intake until the date of progression or death for any cause |
| Measure: | Duration of response (DOR) |
| Time Frame: | Screening, every 8 weeks; up to 2 years |
| Safety Issue: | |
| 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 |
| Measure: | Duration of clinical benefit |
| Time Frame: | Screening, every 8 weeks; up to 2 years |
| Safety Issue: | |
| 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 |
| Measure: | Overall Survival (OS) |
| Time Frame: | Continuously; up to 2 years |
| Safety Issue: | |
| Description: | From the date of first drug intake to the date of death for any cause |
| Measure: | Tumor growth kinetics |
| Time Frame: | Screening, every 8 weeks; up to 2 years |
| Safety Issue: | |
| Description: | Will be evaluated using the following criteria: tumor size; tumor volume; tumor growth |
| Measure: | Incidence of adverse events (AEs), clinical laboratory abnormalities, and dose modifications |
| Time Frame: | Continuously; up to 2 years |
| Safety Issue: | |
| Description: | |
| Measure: | PK parameters of lucitanib |
| Time Frame: | Cycle 1 Day 14 and 28, Cycle 2 Day 28, Cycle 3 Day 28 |
| Safety Issue: | |
| Description: | |
| Measure: | Pharmacogenomic analysis of inter-patients variation in gene encoding ADME involved proteins |
| Time Frame: | Cycle 1 Day 1 |
| Safety Issue: | |
| Description: | |
| Measure: | Pharmacodynamic (PD) evaluation of lucitanib profile |
| Time Frame: | Cycle 1 Day 1 and 14, End of Study |
| Safety Issue: | |
| Description: | Soluble growth factors and other biomarkers, including circulating tumor DNA |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Terminated |
| Lead Sponsor: | Clovis Oncology, Inc. |
Trial Keywords
- FGFR1 amplification
- FGF alteration
- VEGF alteration
- PDGF alteration
- Tyrosine kinase inhibitor
- VEGFR inhibitor
- FGFR inhibitor
- PDGFR inhibitor
- VEGFR-FGFR inhibitor
Last Updated
July 29, 2019
