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

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability and efficacy of SU011248 in patients with non-small cell lung cancer with brain metastases.

Official Title
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A Phase 2 Efficacy And Safety Study Of SU011248 In Patients With Non-Small Cell Lung Cancer And Brain Metastases

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with radiologically proven brain metastases secondary to non-small cell lung cancer Received previous whole brain radiation therapy and none, 1 or 2 prior systemic therapy for the treatment of advanced/metastatic non-small cell lung cancer Exclusion Criteria: Patients with brainstem lesions, spinal cord compression. carcinomatous meningitis, or leptomeningeal disease. Brain metastases >4 cm in any linear direction Intracranial or intratumoral hemorrhage

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sunitinib<br> | Drug: Sunitinib<br>* Sunitinib 37.5 mg daily by oral capsule in a continuous regimen until progression or unacceptable toxicity<br>* Other names: Sutent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | 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]). | Baseline, Day 1 of Week 5, 9, 17, 25, 33, and 41 to tumor progression or death (up to 1 year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Tumor Progression (TTP) | 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. | Baseline, Day 1 of Week 5, 9, 17, 25, 33, and 41 to tumor progression (up to 1 year) | 
| Time to Neurological Progression (TNP) | 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. | Baseline, Day 28 to focal neurological deficit (up to 1 year) | 
| Number of Participants With Objective Disease Response | 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. | Baseline and Day 1 of Week 5, 9, 17, 25, 33, 41, and 49 | 
| Time to Objective Intracranial Progression | 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. | Baseline, Day 1 of Week 5, 9, 17, 25, 33, and 41 to intracranial tumor progression (up to 1 year) | 
| Number of Participants With Intracranial Objective Disease Response | 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. | Baseline and Day 1 of Week 5, 9, 17, 25, 33, 41, and 49 | 
| Duration of Response (DR) | 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. | Day 7 of Week 4 and every 4 weeks up to 1 year | 
| Overall Survival (OS) | OS calculated as: (date of death minus date of first dose plus 1)divided by 30.4. | Baseline until death (up to 1 year) | 
| Percentage of Participants Surviving at 1 Year | Percentage of those surviving at end of 1 year from the first dose of study treatment. | Year 1 | 
| Number of Deaths Due to Intracranial Versus Systemic Progression | Number of deaths determined to be intracranial versus systemic progression, according to investigators'assessment. | Baseline until death (up to 1 year) | 
| Change From Baseline in Functional Assessment of Cancer Therapy/National Comprehensive Cancer Network (FACT/NCCN) Lung Symptom Index (FLSI) Score | 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. | Baseline, Day 1 of Week 5 and every 4 weeks to end of treatment (up to 1 year) | 
| Change From Baseline in FACT/NCCN Brain Symptom Index (FBrSI) Score | 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. | Baseline, Day 1 of Week 5 and every 4 weeks to end of treatment (up to 1 year) | 
| Trough Plasma Concentrations (Ctrough) of Sunitinib | 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. | Day 1 of Week 5, 9, and 13 | 
| Ctrough of Sunitinib Metabolite (SU012662) | 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. | Day 1 of Week 5, 9, and 13 | 
| Correlation of Polymorphisms in c-Kit, Flt-3 and c-Fms With Blood Counts | A blood sample (6mL) collected before treatment with Sunitinib and used to isolate deoxyribonucleic acid (DNA). These samples were not anonymized. | Day 1 prior to dosing | 
| Percentage of Participants by Ribonucleic Acid (RNA) Expression Profile | 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). | Day 1 of Week 1 and every 4 weeks up to 1 year | 
| PFS in Subgroups Defined by RNA Expression Profiles of Tumors | 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. | Day 1 of Week 1 and every 4 weeks up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brain metastases, Sunitinib, Phase 2