Study Tests The Safety And Effectiveness Of SU011248 In Patients With Non-Small Cell Lung Cancer Having Brain Metastases

Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. Since day of first dose of medication and day criteria for progression were met, were each counted as a full day, 1 day was added to each calculation. PFS calculated as (first event date minus date of first dose of study medication plus 1) divided by 7.02. Used 7.02 days because it equals(=) 365 days per year divided by 52 weeks per year. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]).

Time frame: Baseline, Day 1 of Week 5, 9, 17, 25, 33, and 41 to tumor progression or death (up to 1 year)

Population: Intent-to-treat (ITT): all participants enrolled in the study who received at least 1 dose of study medication.

Change from baseline in FBrSI Score was calculated Day 1 of Cycle 2 to 13. Each cycle = 28 days. Scores ranged from 0 to 60. Higher scores indicated better outcomes.

Time frame: Baseline, Day 1 of Week 5 and every 4 weeks to end of treatment (up to 1 year)

Population: ITT population of participants with post baseline patient-reported outcome data

Change from baseline in FLSI Score was calculated Day 1 of Cycle 2 to 13. Each cycle = 28 days. Scores ranged from 0 to 24. Higher scores indicated better outcomes.

Time frame: Baseline, Day 1 of Week 5 and every 4 weeks to end of treatment (up to 1 year)

Population: ITT population of participants with post baseline patient-reported outcome data

A blood sample (6mL) collected before treatment with Sunitinib and used to isolate deoxyribonucleic acid (DNA). These samples were not anonymized.

Time frame: Day 1 prior to dosing

Population: ITT. c-Kit, Flt-3 and c-Fms with blood count samples collected; however, no statistical analyses performed since power was insufficient.

A single blood sample (4 mL) collected pre-dose on Day 1 of Cycles 2, 3, and 4 to determine Ctrough of Sunitinib and its metabolite SU12662. Each cycle = 28 days. Ctrough defined as plasma concentration prior to study drug administration. Trough plasma concentrations were dose-corrected.

Time frame: Day 1 of Week 5, 9, and 13

Population: ITT participants who had pharmacokinetic results for at least 1 day. Ctrough only calculated for subgroup of participants with observations (non-missing concentrations). n = number of participants with evaluable data.

DR defined as difference in weeks between first date criteria for progression occurred, or participant died due to any cause and first date that criteria for a PR or CR were met and subsequently confirmed ≥4 weeks later. Since day criteria for PR or CR were met and first day criteria for progression occurred (or participant died) were each counted as a full day, 1 day was added to each calculation. DR (in weeks) calculated as (first date of PD or death minus first date of CR or PR that was subsequently confirmed plus 1) divided by 7.02.

Time frame: Day 7 of Week 4 and every 4 weeks up to 1 year

Population: ITT. DR only calculated for the subgroup of participants with an objective tumor response.

Number of deaths determined to be intracranial versus systemic progression, according to investigators'assessment.

Time frame: Baseline until death (up to 1 year)

Population: ITT

Intracranial objective disease response defined as participants with confirmed CR or PR, according to WHO criteria. CR defined as disappearance of all enhancing tumor. PR defined as a ≥50% reduction from baseline in sum of the products of all enhancing tumors.

Time frame: Baseline and Day 1 of Week 5, 9, 17, 25, 33, 41, and 49

Population: ITT with measurable intracranial disease at baseline.

Objective disease response defined as participants with confirmed complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST). CR defined as disappearance of all target lesions. PR defined as ≥30% decrease in sum of longest dimensions of target lesions taking as a reference the baseline sum longest dimensions.

Time frame: Baseline and Day 1 of Week 5, 9, 17, 25, 33, 41, and 49

Population: ITT with measurable disease at baseline.

OS calculated as: (date of death minus date of first dose plus 1)divided by 30.4.

Time frame: Baseline until death (up to 1 year)

Population: ITT. In the absence of confirmation of death, survival time was censored to last date of known contact.

Tumor samples were not anonymized. RNA expression profile was to include colony-stimulating factor 1 receptor (CSF-1R), platelet-derived growth factor receptor alpha and beta (PDGFRalpha and PDGFRbeta), vascular endothelial growth factor (VEGF), VEGF-C, VEGF receptor 1, 2, and 3 (VEGFR1, VEGFR2, and VEGFR3), fibroblast growth factor (FGF), FMS-like tyrosine kinase 3 (FLT3), KIT (stem cell factor receptor), and RET (rearranged during transfection).

Time frame: Day 1 of Week 1 and every 4 weeks up to 1 year

Population: ITT. Only 4 RNA samples were collected and no statistical analyses performed.

Percentage of those surviving at end of 1 year from the first dose of study treatment.

Time frame: Year 1

Population: ITT

PFS defined as time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was to be determined in subgroups defined by RNA Gene expression (CSF-1R, PDGFRalpha, PDGFRbeta, VEGF, VEGF-C, VEGFR1, VEGFR2, VEGFR3, FGF, FLT3, KIT, and RET) level (low/high relative to expression of Glyceraldehyde-3-Phosphate Dehydrogenase \[GAPDH\] reference gene). PFS calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7.02.

Time frame: Day 1 of Week 1 and every 4 weeks up to 1 year

Population: ITT. Only 4 RNA samples were collected and no statistical analyses performed.

Time in weeks between first date criteria for focal neurological deficit were met and date of first dose of medication. Criteria for focal neurological deficit included speech or language difficulties, vision changes, loss of coordination or fine motor control, and seizures. Since day of first dose of medication and day criteria for focal neurological deficit were met were each counted as a full day, 1 day was added to each calculation. TNP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7.02.

Time frame: Baseline, Day 28 to focal neurological deficit (up to 1 year)

Population: ITT

Time in weeks from start of study treatment to first documentation of objective intracranial tumor progression. Intracranial tumor progression defined as ≥25% increase from smallest size in sum of products of all enhancing tumors or appearance of any new tumor, according to World Health Organization (WHO) criteria. Since day of first dose of medication and day criteria for progression were met, were each counted as a full day, 1 day added to each calculation. Time to Objective Intracranial Progression = (first event date minus the date of first dose of study medication plus 1) divided by 7.02.

Time frame: Baseline, Day 1 of Week 5, 9, 17, 25, 33, and 41 to intracranial tumor progression (up to 1 year)

Population: ITT

Time from start of study treatment to first documentation of objective tumor progression. Tumor progression defined as greater than or equal to 20 percent (≥20%) increase in sum of longest dimensions of target lesions using as reference smallest sum of longest dimensions recorded since treatment started, or unequivocal progression of existing non-target lesions, or appearance of ≥1 new lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST). TTP = (first event date minus date of first dose of study medication plus 1) divided by 7.02.

Time frame: Baseline, Day 1 of Week 5, 9, 17, 25, 33, and 41 to tumor progression (up to 1 year)

Population: ITT

A single blood sample (4 milliliters \[mL\]) collected pre-dose on Day 1 of Cycles 2, 3, and 4 to determine Ctrough of Sunitinib and its metabolite SU12662. Each cycle = 28 days. Ctrough defined as plasma concentration prior to study drug administration. Trough plasma concentrations were dose-corrected.

Time frame: Day 1 of Week 5, 9, and 13

Population: ITT participants who had pharmacokinetic results for at least 1 day. Ctrough only calculated for subgroup of participants with observations (non-missing concentrations). n = number of participants with evaluable data.