A Study Of Crizotinib Plus VEGF Inhibitor Combinations In Patients With Advanced Solid Tumors.

Summary

Despite the success of anti-angiogenic therapy in multiple treatment settings, a fraction of patients are refractory to vascular endothelial growth factor (VEGF) inhibitor treatment while the majority of patients will eventually develop evasive resistance and exhibit disease progression while on therapy. It is proposed that mesenchymal-epithelial transition factor (c-MET) and its ligand hepatocyte growth factor (HGF or scatter factor) contribute significantly to VEGF inhibitor resistance such that combining a c-MET inhibitor with a VEGF inhibitor will provide additional clinical activity compared to VEGF inhibitor alone. This hypothesis will be tested using the cMET/ALK inhibitor, crizotinib, in combination with individual VEGF inhibitors. Three combinations will be prioritized, namely crizotinib plus axitinib, crizotinib plus sunitinib and crizotinib plus bevacizumab, with a fourth combination, crizotinib plus sorafenib to be tested only if crizotinib does not combine with either axitinib and/or sunitinib.

Conditions

• Carcinoma, Renal Cell
• Glioblastoma
• Carcinoma, Hepatocellular

Interventions

DRUG

Crizotinib plus VEGF inhibitor combinations

Three combinations will be prioritized, namely crizotinib plus axitinib, crizotinib plus sunitinib and crizotinib plus bevacizumab, with a fourth combination, crizotinib plus sorafenib to be tested only if crizotinib does not combine with either axitinib and/or sunitinib. All study drugs are tablets or capsules except for bevacizumab which is parenteral (intravenous). Dosage, frequency and duration to be determined.

DRUG

Crizotinib plus axitinib

Study drugs are tablets or capsules; dosage, frequency and duration to be determined.

DRUG

Crizotinib plus sunitinib

Study drugs are tablets or capsules; dosage, frequency and duration to be determined.

DRUG

Crizotinib plus axitinib

Study drugs are tablets or capsules; dosage, frequency and duration to be determined.

DRUG

Crizotinib plus sunitinib

Study drugs are tablets or capsules; dosage, frequency and duration to be determined.

DRUG

Crizotinib plus bevacizumab

Study drugs are tablets or capsules except for bevacizumab which is parenteral (intravenous). Dosage, frequency and duration to be determined.

DRUG

Crizotinib plus sorafenib

Study drugs are tablets or capsules; dosage, frequency and duration to be determined.

Sponsors & Collaborators

• Pfizer

  lead INDUSTRY

Principal Investigators

• Pfizer CT.gov Call Center · Pfizer

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-12-31

Primary Completion

2013-11-30

Completion

2013-11-30