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

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00372775
First received: September 5, 2006
Last updated: January 27, 2011
Last verified: January 2011
  Purpose

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


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: Sunitinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Efficacy And Safety Study Of SU011248 In Patients With Non-Small Cell Lung Cancer And Brain Metastases

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: Baseline, Day 1 of Week 5, 9, 17, 25, 33, and 41 to tumor progression or death (up to 1 year) ] [ Designated as safety issue: No ]
    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]).


Secondary Outcome Measures:
  • Time to Tumor Progression (TTP) [ Time Frame: Baseline, Day 1 of Week 5, 9, 17, 25, 33, and 41 to tumor progression (up to 1 year) ] [ Designated as safety issue: No ]
    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 to Neurological Progression (TNP) [ Time Frame: Baseline, Day 28 to focal neurological deficit (up to 1 year) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Objective Disease Response [ Time Frame: Baseline and Day 1 of Week 5, 9, 17, 25, 33, 41, and 49 ] [ Designated as safety issue: No ]
    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 to Objective Intracranial Progression [ Time Frame: Baseline, Day 1 of Week 5, 9, 17, 25, 33, and 41 to intracranial tumor progression (up to 1 year) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Intracranial Objective Disease Response [ Time Frame: Baseline and Day 1 of Week 5, 9, 17, 25, 33, 41, and 49 ] [ Designated as safety issue: No ]
    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.

  • Duration of Response (DR) [ Time Frame: Day 7 of Week 4 and every 4 weeks up to 1 year ] [ Designated as safety issue: No ]
    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.

  • Overall Survival (OS) [ Time Frame: Baseline until death (up to 1 year) ] [ Designated as safety issue: No ]
    OS calculated as: (date of death minus date of first dose plus 1)divided by 30.4.

  • Percentage of Participants Surviving at 1 Year [ Time Frame: Year 1 ] [ Designated as safety issue: No ]
    Percentage of those surviving at end of 1 year from the first dose of study treatment.

  • Number of Deaths Due to Intracranial Versus Systemic Progression [ Time Frame: Baseline until death (up to 1 year) ] [ Designated as safety issue: Yes ]
    Number of deaths determined to be intracranial versus systemic progression, according to investigators'assessment.

  • Change From Baseline in Functional Assessment of Cancer Therapy/National Comprehensive Cancer Network (FACT/NCCN) Lung Symptom Index (FLSI) Score [ Time Frame: Baseline, Day 1 of Week 5 and every 4 weeks to end of treatment (up to 1 year) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in FACT/NCCN Brain Symptom Index (FBrSI) Score [ Time Frame: Baseline, Day 1 of Week 5 and every 4 weeks to end of treatment (up to 1 year) ] [ Designated as safety issue: No ]
    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.

  • Trough Plasma Concentrations (Ctrough) of Sunitinib [ Time Frame: Day 1 of Week 5, 9, and 13 ] [ Designated as safety issue: No ]
    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.

  • Ctrough of Sunitinib Metabolite (SU012662) [ Time Frame: Day 1 of Week 5, 9, and 13 ] [ Designated as safety issue: No ]
    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.

  • Correlation of Polymorphisms in c-Kit, Flt-3 and c-Fms With Blood Counts [ Time Frame: Day 1 prior to dosing ] [ Designated as safety issue: No ]
    A blood sample (6mL) collected before treatment with Sunitinib and used to isolate deoxyribonucleic acid (DNA). These samples were not anonymized.

  • Percentage of Participants by Ribonucleic Acid (RNA) Expression Profile [ Time Frame: Day 1 of Week 1 and every 4 weeks up to 1 year ] [ Designated as safety issue: No ]
    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).

  • PFS in Subgroups Defined by RNA Expression Profiles of Tumors [ Time Frame: Day 1 of Week 1 and every 4 weeks up to 1 year ] [ Designated as safety issue: No ]
    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.


Enrollment: 66
Study Start Date: March 2007
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sunitinib Drug: Sunitinib
Sunitinib 37.5 mg daily by oral capsule in a continuous regimen until progression or unacceptable toxicity
Other Name: Sutent

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00372775

Locations
United States, Connecticut
Pfizer Investigational Site
Norwalk, Connecticut, United States, 06856
United States, Florida
Pfizer Investigational Site
Cocoa Beach, Florida, United States, 32931
Pfizer Investigational Site
Merritt Island, Florida, United States, 32952
Pfizer Investigational Site
Titusville, Florida, United States, 32796
United States, Missouri
Pfizer Investigational Site
Creve Coeur, Missouri, United States, 63141
Pfizer Investigational Site
St. Louis, Missouri, United States, 63110
Pfizer Investigational Site
St. Louis, Missouri, United States, 63110-1094
Pfizer Investigational Site
St. Peters, Missouri, United States, 63376
United States, New Jersey
Pfizer Investigational Site
Basking Ridge, New Jersey, United States, 07920
United States, New York
Pfizer Investigational Site
Commack, New York, United States, 11725
Pfizer Investigational Site
New York, New York, United States, 10022
United States, Pennsylvania
Pfizer Investigational Site
Sayre, Pennsylvania, United States, 18840
United States, Texas
Pfizer Investigational Site
Austin, Texas, United States, 78745
Pfizer Investigational Site
Austin, Texas, United States, 78705
Pfizer Investigational Site
Austin, Texas, United States, 78758
Pfizer Investigational Site
Austin, Texas, United States, 78759
Pfizer Investigational Site
Round Rock, Texas, United States, 78664
France
Pfizer Investigational Site
Pessac, Be1 04495, France, 33604
Pfizer Investigational Site
Marseille Cedex 09, France, 13009
Pfizer Investigational Site
Saint-Priest en Jarez Cedex, France, 42271
Pfizer Investigational Site
Toulouse cedex 9, France, 31059
Italy
Pfizer Investigational Site
Bologna, Italy, 40139
Pfizer Investigational Site
Genova, Italy, 16132
Pfizer Investigational Site
Orbassano (TO), Italy, 10043
Pfizer Investigational Site
Roma, Italy, 00151
Spain
Pfizer Investigational Site
Madrid, Spain, 28046
Pfizer Investigational Site
Valencia, Spain, 46014
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer Inc
ClinicalTrials.gov Identifier: NCT00372775     History of Changes
Other Study ID Numbers: A6181092
Study First Received: September 5, 2006
Results First Received: December 8, 2010
Last Updated: January 27, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
brain metastases
Sunitinib
Phase 2

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasm Metastasis
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014