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

January 27, 2011 updated by: Pfizer

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

66

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Marseille Cedex 09, France, 13009
        • Pfizer Investigational Site
      • Saint-Priest en Jarez Cedex, France, 42271
        • Pfizer Investigational Site
      • Toulouse cedex 9, France, 31059
        • Pfizer Investigational Site
    • Be1 04495
      • Pessac, Be1 04495, France, 33604
        • Pfizer Investigational Site
  • Italy
      • Bologna, Italy, 40139
        • Pfizer Investigational Site
      • Genova, Italy, 16132
        • Pfizer Investigational Site
      • Orbassano (TO), Italy, 10043
        • Pfizer Investigational Site
      • Roma, Italy, 00151
        • Pfizer Investigational Site
  • Spain
      • Madrid, Spain, 28046
        • Pfizer Investigational Site
      • Valencia, Spain, 46014
        • Pfizer Investigational Site
  • United States
    • Connecticut
      • Norwalk, Connecticut, United States, 06856
        • Pfizer Investigational Site
    • Florida
      • Cocoa Beach, Florida, United States, 32931
        • Pfizer Investigational Site
      • Merritt Island, Florida, United States, 32952
        • Pfizer Investigational Site
      • Titusville, Florida, United States, 32796
        • Pfizer Investigational Site
    • Missouri
      • 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
        • Pfizer Investigational Site
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Pfizer Investigational Site
    • New York
      • Commack, New York, United States, 11725
        • Pfizer Investigational Site
      • New York, New York, United States, 10022
        • Pfizer Investigational Site
    • Pennsylvania
      • Sayre, Pennsylvania, United States, 18840
        • Pfizer Investigational Site
    • Texas
      • Austin, Texas, United States, 78705
        • Pfizer Investigational Site
      • Austin, Texas, United States, 78745
        • Pfizer Investigational Site
      • Austin, Texas, United States, 78759
        • Pfizer Investigational Site
      • Austin, Texas, United States, 78758
        • Pfizer Investigational Site
      • Round Rock, Texas, United States, 78664
        • Pfizer Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sunitinib
Drug: Sunitinib
Sunitinib 37.5 mg daily by oral capsule in a continuous regimen until progression or unacceptable toxicity
Other Names:
  • Sutent

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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 Frame: Baseline, Day 1 of Week 5, 9, 17, 25, 33, and 41 to tumor progression (up to 1 year)
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 Frame: Baseline, Day 28 to focal neurological deficit (up to 1 year)
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
Time Frame: Baseline and Day 1 of Week 5, 9, 17, 25, 33, 41, and 49
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 Frame: Baseline, Day 1 of Week 5, 9, 17, 25, 33, and 41 to intracranial tumor progression (up to 1 year)
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
Time Frame: Baseline and Day 1 of Week 5, 9, 17, 25, 33, 41, and 49
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)
Time Frame: Day 7 of Week 4 and every 4 weeks up to 1 year
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)
Time Frame: Baseline until death (up to 1 year)
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
Time Frame: Year 1
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
Time Frame: Baseline until death (up to 1 year)
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
Time Frame: Baseline, Day 1 of Week 5 and every 4 weeks to end of treatment (up to 1 year)
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
Time Frame: Baseline, Day 1 of Week 5 and every 4 weeks to end of treatment (up to 1 year)
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
Time Frame: Day 1 of Week 5, 9, and 13
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)
Time Frame: Day 1 of Week 5, 9, and 13
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
Time Frame: Day 1 prior to dosing
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
Time Frame: Day 1 of Week 1 and every 4 weeks up to 1 year
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
Time Frame: Day 1 of Week 1 and every 4 weeks up to 1 year
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

December 1, 2009

Study Completion (Actual)

December 1, 2009

Study Registration Dates

First Submitted

September 5, 2006

First Submitted That Met QC Criteria

September 5, 2006

First Posted (Estimate)

September 7, 2006

Study Record Updates

Last Update Posted (Estimate)

February 24, 2011

Last Update Submitted That Met QC Criteria

January 27, 2011

Last Verified

January 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A6181092

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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