Study of Low Dose Chemotherapy Plus Sorafenib as Initial Therapy for Patients With Advanced Non-Squamous Cell NSCLC

Non Small Cell Lung Cancer Clinical Trial

Official title: Pilot Phase IIa Study of Metronomic Chemotherapy With Taxotere (Docetaxel) Plus Nexavar (Sorafenib) as First-Line Therapy in Performance Status-2 Patients With Advanced Non-Squamous Cell Non-Small Cell Lung Cancer

Status Terminated

Clinical Trial Summary

The purpose of this study is to assess the 2-month progression-free survival in patients with advanced or metastatic, non-squamous cell lung cancer treated with weekly low dose docetaxel in combination with a biologic dose of sorafenib.

Clinical Trial Description

The median survival of untreated advanced stage NSCLC is 5-6 months (2,3). Patients with poor performance status due to malignancy or co-morbidities have a poorer survival. This group of patients is underrepresented in clinical trials and may not receive chemotherapy due to fear of increased toxicities with systemic chemotherapy. The overall median survival of patients with advanced NSCLC treated with first-line platinum-based doublets is less than 12 months (8 10 months) with a 1-year and 2-year survival rate of 33% and 11%, respectively (4 6). No chemotherapy regimen has a significant advantage over the others in the treatment of advanced NSCLC. Agents targeting epidermal growth factor receptor, matrix metalloproteinase, farnesyl transferase, protein kinase C and retinoic X receptor have so far shown no survival benefit in combination with chemotherapy in advanced NSCLC (7-13). Docetaxel has activity in NSCLC in both first line and second line settings. In poor performance status patients or elderly patients, single agent chemotherapy is recommended. Weekly docetaxel administration is well tolerated and has lesser incidence of hematologic toxicity with no difference in overall survival when compared to patients receiving higher doses (75 mg/m2) q 3 weeks (14-18). There is an increased need for better strategies to improve survival as well as reduce regimen related toxicity for this large group of patients. The use of targeted therapy as well as low dose-protracted chemotherapy (metronomic chemotherapy) needs evaluation as such therapies have a better toxicity profile.

Sorafenib (BAY 49-bursts of toxic maximum tolerated dose (MTD) chemotherapy interspersed with long breaks, there is now a shift in thinking towards the view that more compressed or accelerated schedules of drug administration using much smaller individual doses than the MTD would be more effective; not only in terms of reducing certain toxicities, but perhaps even in improving antitumor effect as well. Moreover, some of these dosing/scheduling strategies are ideally suited to combining chemotherapeutic agents with many of the new targeted biologic drugs. The most recent refinement of this concept is called "metronomic" chemotherapy, which refers to the frequent administration of cytotoxic chemotherapeutic agents at doses significantly below the MTD, with no prolonged drug-free breaks. ;

Study Design

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer
• Non Squamous Cell Lung Cancer

• NCT number: NCT00801801
• Study type: Interventional
• Source: University of Alabama at Birmingham
• Status: Terminated
• Phase: Phase 2
• Start date: January 2008
• Completion date: March 2011