This phase II trial is studying how well saracatinib works in treating patients with recurrent, stage IIIB or stage IV non-small cell lung cancer previously treated with combination chemotherapy that included cisplatin or carboplatin. Saracatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. Assess the rate of disease control (i.e., lack of disease progression, a combined rate of objective complete and partial response, and stable disease) for at least 4 cycles of therapy in patients with AZD0530 (saracatinib) in patients with advanced non-small cell lung cancer that had previously been treated with platinum-based combination chemotherapy. SECONDARY OBJECTIVES: I. To assess the objective response rate (complete and partial response), stable disease rate, duration of response or stable disease, progression-free, median and 6 month overall survival rates, safety and tolerability of this treatment. TERTIARY OBJECTIVES: I. To evaluate potential predictive markers by assessing pretreatment intratumoral levels of src, Y419 phospho-src (P-Src) and c-terminal src kinase (Csk) in archival tumor biopsies. OUTLINE: This is a multicenter study. Patients receive saracatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Tumor tissue samples are collected at baseline and at 2 weeks after beginning treatment and are analyzed for c-Src protein expression and activity by immunofluorescence staining. P-glycoprotein levels and phosphorylation of focal adhesion kinase (FAK), paxillin, caveolin, and Stat-3 are also measured using tumor tissue samples. Blood samples are also used to measure levels of vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay (ELISA). After completion of study treatment, patients are followed every 4 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
Given PO
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada
The Ottawa Hospital Cancer Centre (Ottawa Health Research Institute) Civic Campus
Ottawa, Ontario, Canada
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada
McGill University Department of Oncology
Montreal, Quebec, Canada
Rate of Disease Control (Freedom From Disease Progression)
Lack of disease progression, a combined rate of objective complete (disapprearance of all target lesions) and partial responses (\>= 30% decrease in sum of longest diameter of target lesions) and stable disease as determined by Response Evaluation Criteria in Solid Tumours (RECIST 1.0) for at least 4 cycles (16 weeks) of therapy. Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible.
Time frame: 112 days
Objective Response Rate (Complete and Partial Response)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions Overall Response (OR) = CR + PR Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible.
Time frame: From the start of the treatment until the criteria for response are met
Stable Disease Rate
Stabilization of disease for atleast 4 cycles, leading to disease control Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible.
Time frame: From the start of the treatment until the criteria for progression are met, assessed up to 1 year
Duration of Response or Stable Disease
Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible.
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Time frame: From first response until the criteria for progression are met, assessed up to 1 year
Median Progression-free Survival
The Kaplan-Meier method will be used.
Time frame: From the date of study enrollment to the time the criteria for disease progression are met, death or last contact, or the last tumor assessment before the initiation of further anticancer therapy, assessed up to 1 year
Progression-free Survival
Progression free survival (PFS) is defined as the time from randomization to the date of first documented disease progression or death from any cause The Kaplan-Meier method will be used.
Time frame: 6 months
Median Overall Survival
The Kaplan-Meier method will be used.
Time frame: Up to 1 year
Overall Survival
One year overall survival rate The Kaplan-Meier method will be used.
Time frame: 1 year