Pilot Phase II Study of Metronomic Chemotherapy in Combination With Avastin in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Paclitaxel
- Conditions
- Non-Small Cell Lung Cancer
- Sponsor
- University of Alabama at Birmingham
- Enrollment
- 39
- Locations
- 1
- Primary Endpoint
- Progression-Free Survival (PFS)
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This study is being done to determine the overall progression-free survival (PFS) in patients with advanced or metastatic (Stage IIIB - pleural effusion/IV), non-squamous histology NSCLC treated with metronomic chemotherapy plus Avastin. Also, currently there are no defined markers that predict for clinical benefit to Avastin. Preliminary studies show that there are several observations that support the concept of metronomic chemotherapy with or without the combination of an anti-angiogenic agent. The metronomic chemotherapy with Avastin was shown to enhance the clinical endpoints of the study (response rate and progressive-free survival). Proof of metronomic scheduling requires the development of appropriate intermediate surrogate markers. Several markers will be assessed.
Detailed Description
This is a non-randomized, open-label, pilot Phase II study of metronomic chemotherapy plus Avastin in chemo naïve subjects with advanced non-squamous, non-small cell carcinoma of the lung. The primary endpoint of this study is to assess the overall progression-free survival. Subjects will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks, and Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy will be expressed as a 4-week cycle. Tumor response to treatment will be evaluated every 8 weeks. Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with Avastin will then continue until disease progression, intolerable toxicity or withdrawal of consent. Potential biologic parameters to monitor anti-tumor activity of metronomic chemotherapy will be evaluated in 10 subjects. These biomarkers include: sequential determination of blood levels of VEGF, VEGFR2, thrombospondin-1, E-selectin, ICAM-1, and circulating endothelial cells and endothelial precursor cells.
Investigators
Francisco Robert,MD
Professor
University of Alabama at Birmingham
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Paclitaxel and Gemcitabine + Avastin
Patients will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks which constitutes one cycle (4 weeks). Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with Avastin will continue until disease progression, intolerable toxicity, or withdrawal of consent.
Intervention: Paclitaxel
Paclitaxel and Gemcitabine + Avastin
Patients will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks which constitutes one cycle (4 weeks). Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with Avastin will continue until disease progression, intolerable toxicity, or withdrawal of consent.
Intervention: Gemcitabine
Paclitaxel and Gemcitabine + Avastin
Patients will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks which constitutes one cycle (4 weeks). Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with Avastin will continue until disease progression, intolerable toxicity, or withdrawal of consent.
Intervention: Avastin
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: Baseline to 24 months
Progression Free Survival is defined as the number of days from the day the subject started treatment to the day the subject experiences disease progression in accordance with the Response Evaluation Criteria Solid Tumors (RECIST v1.0). The RECIST criteria indicates progression as a 20% increase in the total tumor measurement over nadir value or the appearance of new lesions.
Secondary Outcomes
- Number of Participants With Adverse Events(Baseline through duration of treatment an average of 1 year)
- Overall Survival (OS)(Baseline up to 84 months)
- Objective Response Rate(Baseline up to 12 months)