Vatalanib in malignant mesothelioma: a phase II trial by the Cancer and Leukemia Group B (CALGB 30107)

Lung Cancer. 2012 Jun;76(3):393-6. doi: 10.1016/j.lungcan.2011.11.014. Epub 2011 Dec 22.

Abstract

Introduction: The Cancer and Leukemia Group B (CALGB) conducted a multi-center phase II trial to evaluate the efficacy and safety of vatalanib in previously untreated patients with malignant mesothelioma and to evaluate potential biomarkers of disease response (CALGB 30107).

Methods: Treatment consisted of vatalanib 1250 mg given orally once daily. CT scans were obtained at baseline and every 6 weeks thereafter. Baseline serum levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), thrombospondin-1 (TSP-1), and mesothelin were obtained. The primary endpoint was 3-month progression-free survival (PFS).

Results: Forty-seven patients enrolled at 19 centers. The median age was 75 years, and the majority of patients (79%) had an ECOG performance status of 1. Tumors were classified as epithelial (77%), sarcomatoid (10%), or mixed (9%) histology. Toxicity was mild; the most common grade 3/4 adverse events were neutropenia (2%), nausea (15%), elevated alanine aminotransferase (11%), hypertension (2%), and gastrointestinal bleeding (2%). Partial responses were observed in 6% of patients and stable disease in 72% of patients. The 3-month PFS rate was 55% (95% CI: 40%, 68%). The median PFS was 4.1 months. Median overall survival was 10.0 months. There was no correlation between serum levels of VEGF, PDGF, TSP-1, or mesothelin and treatment response, PFS, or survival.

Conclusions: Vatalanib as a single agent with this dose and schedule does not warrant further study in this disease.

Trial registration: ClinicalTrials.gov NCT00053885.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / blood
  • Female
  • GPI-Linked Proteins / blood
  • Humans
  • Male
  • Mesothelin
  • Mesothelioma / blood
  • Mesothelioma / drug therapy*
  • Mesothelioma / mortality
  • Middle Aged
  • Phthalazines / administration & dosage
  • Phthalazines / adverse effects
  • Phthalazines / therapeutic use*
  • Platelet-Derived Growth Factor
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyridines / administration & dosage
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Survival Analysis
  • Thrombospondin 1 / blood
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • GPI-Linked Proteins
  • Phthalazines
  • Platelet-Derived Growth Factor
  • Protein Kinase Inhibitors
  • Pyridines
  • Thrombospondin 1
  • Vascular Endothelial Growth Factor A
  • vatalanib
  • Mesothelin

Associated data

  • ClinicalTrials.gov/NCT00053885