Pazopanib in Relapsed and Refractory Small Cell Lung Cancer

SCLC Clinical Trial

Official title: A Phase II Trial of Pazopanib, in Relapsed and Refractory Small Cell Lung Cancer (SCLC)

Status Completed

Clinical Trial Summary

Investigators propose to study the single agent activity of pazopanib in a Phase II trial of patients with relapsed or refractory small cell lung cancer. Because these patients have very limited treatment options, use of an investigational agent in this patient population is supported by current National Comprehensive Cancer Network guidelines. Using correlative biologic studies to evaluate the anti angiogenic activity of pazopanib in the absence of concomitant chemotherapy will allow us to delineate the responses due to this drug and the effect on angiogenesis.

Pazopanib dose has been determined to 800 mg once daily per the initial recommended dose approved by FDA and EMA, as monotherapy in advanced Renal Cell Carcinoma

Clinical Trial Description

Small cell lung cancer is a tumor that initially responds to chemotherapy and radiotherapy, however, it is associated with very poor prognosis since the initial response is nearly always followed by relapse and metastasis. The response to subsequent therapy is very limited as is the duration of response in these patients. Patients with SCLC have high rates of metastases at presentation suggesting that angiogenesis is particularly important in this cancer, furthermore studies have shown that microvessel density and VEGF expression in SCLC tumor samples correlate with development of metastases and poor prognosis. Furthermore VEGF expression was the only factor that retained a significant inverse correlation with survival when assessed in a multivariate analysis.

Pazopanib is a potent, small molecule competitive inhibitor of the tyrosine kinase activity of (VEGFR 1), VEGFR 2, VEGFR 3, platelet derived growth factor (PDGF), and c kit, capable of inhibiting downstream signalling from these receptors. The IC50 of pazopanib against VEGFR 2 is 10nm, and the IC50 against VEGFR 1 is <50nm. Currently a number of studies is underway for the evaluation of pazopanib in the treatment NSCLC. Administering pazopanib to patients with relapsed SCLC offers an attractive choice in patients with very limited therapeutic choices. The high rate of metastasis highlights the need for alternative treatments that act directly on the growth and invasion of tumors and subsequent development of metastases, rather than solely on cell proliferation. ;

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• SCLC
• Small Cell Lung Carcinoma

• NCT number: NCT01713296
• Study type: Interventional
• Source: Hellenic Oncology Research Group
• Status: Completed
• Phase: Phase 2
• Start date: November 2011
• Completion date: March 2015