Study of Low Dose Chemotherapy Plus Sorafenib as Initial Therapy for Patients With Advanced Non-Squamous Cell NSCLC
|ClinicalTrials.gov Identifier: NCT00801801|
Recruitment Status : Terminated (Sponsors withdrew funding; preliminary efficacy data was not encouraging.)
First Posted : December 4, 2008
Results First Posted : June 19, 2013
Last Update Posted : May 17, 2017
|Condition or disease||Intervention/treatment||Phase|
|Non Squamous Cell Lung Cancer Non Small Cell Lung Cancer||Drug: Docetaxel + Sorafenib||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||January 2008|
|Primary Completion Date :||October 2009|
|Study Completion Date :||March 2011|
Experimental: Metronomic Docetaxel + Sorafenib
Subjects with advanced non-squamous cell non-small cell lung cancer with poor performance status will receive treatment in this non-randomized, open-label Phase II Study of Metronomic Chemotherapy (docetaxel) plus sorafenib as first-line therapy.
Subjects will be treated with metronomic chemotherapy with low dose docetaxel weekly for 3 out of 4 weeks, and sorafenib will be administered continuously 400 mg bid on a 28 day cycle. Treatment with metronomic chemotherapy will be expressed as a 4-week cycle.
Drug: Docetaxel + Sorafenib
Subjects will be treated with metronomic chemotherapy with low dose docetaxel weekly for 3 out of 4 weeks, and sorafenib will be administered continuously 400 mg bid on a 28 day cycle. Treatment with metronomic chemotherapy will be expressed as a 4-week cycle. Tumor response to treatment will be evaluated after every 8 weeks. Treatment with metronomic chemotherapy and sorafenib will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with sorafenib will then continue until disease progression, intolerable toxicity or withdrawal of consent.
- 2-month Progression-free Survival Rate [ Time Frame: Baseline to 2 months ]Evaluation of the 2-month progression-free survival in poor performance status patients with non-squamous non-small cell lung cancer with the goal to improve 2-month progression free survival from 50% to 70%. The 2-month progression free survival is determined after 8 weeks on treatment. Those patients that had less than 20% increase in the tumor target lesions are considered as progression free survival. The primary endpoint is the percentage of patients that are progression free in 2 months.
- Response Rate in Poor Performance Status Subjects [ Time Frame: 6 months ]To assess response rate and tumor control rate (complete remission + partial remission + stable disease) in poor performance status (PS =2) patients with advanced or metastatic (Stage IIIB - pleural effusion/IV) non-squamous cell-NSCLC treated with metronomic chemotherapy plus sorafenib. The objective response was defined as a percentage of those patients that had 30% or more of tumor regression at any time during treatment. Tumor control rate include the percentage of those patients that have less than 20% increase in the target tumor parameters during treatment (stable disease + partial response + complete response).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00801801
|United States, Alabama|
|University of Alabama at Birmingham|
|Birmingham, Alabama, United States, 35294 - 0104|
|Principal Investigator:||Francisco Robert, M.D.||University of Alabama at Birmingham|