Dasatinib in Advanced Non-small Cell Lung Cancer (NSCL) With Ex Vivo and In Vivo Assessment of Tumor Target Modulation
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase II Study of Dasatinib in Advanced Non-small Cell Lung Cancer With Ex Vivo and In Vivo Assessment of Tumor Target Modulation|
- Number of Participant Progressors vs. Non-progressors With Tumor Response [ Time Frame: 1 year, 4 months ]We planned to assess whether the extent of inhibition of extracellular signal-regulated protein kinase (ERK) phosphorylation in lung cancer cells exposed ex vivo to dasatinib significantly differed between patients categorized as progressors or non-progressors through standard Response Evaluation Criteria In Solid Tumors (RECIST)
- Number of Participants With Response to Dasatinib [ Time Frame: 1 year, 4 months ]We planned to estimate the single agent response rate to dasatinib in this patient population
- Number of Participants With Progression Free Survival (PFS) at 6 Months [ Time Frame: 1 year, 4 months ]We planned to estimate the 6 month progression free survival rate of dasatinib in this patient population.
- Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: 1 year, 4 months ]We evaluated toxicity of dasatinib in this patient population.
- Number of Participant Progressors vs. Non-Progressors With Inhibition Response [ Time Frame: 1 year, 4 months ]We planned to assess whether the extent of inhibition of proto-oncogene tyrosine-protein kinase (SRC) and protein kinase B (Akt) phosphorylation in lung cancer cells exposed ex vivo and in vivo to dasatinib significantly differs between patients categorized as progressors or non-progressors through standard RECIST criteria.
- Correlation Between Extent of Inhibition and Concentration of Dasatinib [ Time Frame: 1 year, 4 months ]We planned to explore whether the extent of inhibition of ERK, SRC and Akt phosphorylation in lung cancer cells exposed ex vivo to dasatinib will correlate with the drug concentration of dasatinib.
- Correlation Between Mutation and Inhibition and to Disease Control Rate and Response [ Time Frame: 1 year, 4 months ]To analyze Kras and epidermal growth factor receptor (EGFR) mutation and their correlation to the ERK pathway inhibition and to disease control rate and response.
|Study Start Date:||March 2009|
|Study Completion Date:||July 2010|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Experimental: Treatment with Dasatinib
Dasatinib 140 mg orally (po) every day starting Day #1, continuous dosing. This dose was chosen based on the current experience in patients with solids tumors who have had prior chemotherapy.
Take tablets of Dasatinib by mouth once a day.
Other Name: SPRYCEL®
Cycle 1 Day 1 (C1D1): Patients will have complete history and physical (H&P), complete blood count (CBC), complete metabolic panel (CMP) and electrocardiogram (EKG) on day 1. Each cycle is 28 days. The C1D1 EKG can be omitted if the patient has no new cardiac symptoms and has not starting taking any medication known to affect QT corrected for heart rate (QTc) prolongation. Any residual toxicity from prior therapy for cancer will be recorded. Blood will be drawn for assessment of serum markers. The patient will begin dasatinib at the starting C1D1 on a daily basis.
Cycle 1 Day 10-20 (C1D10-20): Patients will have a second biopsy to obtain additional tumor material to examine biological effects of dasatinib on signaling pathways. Dasatinib will be taken first thing in the morning and the patient will log the time. Blood will also be drawn for pharmacokinetic assessments of dasatinib levels in plasma and the time recorded. Four FNA aspirates and 2 core biopsies can be obtained either at the bedside for palpable lesions or through appropriate image-guided techniques (CT or US) at the discretion of the treating physician in consultation with radiology. The time of the biopsy will be recorded. One core biopsy should be immediately fixed in formalin and the other core biopsy should be snap frozen in liquid nitrogen.
Cycle 2 Day 1 (C2D1): Patients will be seen by the treating physician and have complete H&P, CBC, and CMP. Blood will be drawn for assessment of serum markers. Toxicity of dasatinib will be assessed. The patient will continue to take daily doses of dasatinib on a daily basis.
Cycle 2 Day 22 (C2D22): Patients will undergo reevaluation for tumor measurements. This assessment can occur on C2D22 ±7 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00858403
|United States, Florida|
|H. Lee Moffitt Cancer Center & Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Eric Haura, M.D.||H. Lee Moffitt Cancer Center and Research Institute|