A Study In Patients With Non-Small Cell Lung Cancer Testing If Erlotinib Plus SU011248 (Sunitinib) Is Better Than Erlotinib Alone (SUN1058)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00265317
First received: December 12, 2005
Last updated: January 31, 2013
Last verified: January 2013
  Purpose

This study will test whether treatment with erlotinib plus SU011248 is better than erlotinib alone in patients with advanced/metastatic lung cancer who have received previous treatment with a platinum-based regimen


Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: erlotinib
Drug: sunitinib
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Phase 2 Study Of Erlotinib With Or Without SU011248 In The Treatment Of Metastatic Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) ] [ Designated as safety issue: No ]
    PFS=time from randomization date to date of first documentation of progressive disease (PD; defined as greater than or equal to [≥]20% increase in sum of longest dimensions of target lesions taking as a reference smallest sum of longest dimensions recorded since first dose or appearance of ≥1 new lesions) or death on-study due to any cause, whichever occurred first based on third party independent imaging review laboratory assessment. PFS calculated as (first event date minus randomization date plus 1) divided by 7.02. Used 7.02 days as it equals 365 days per year divided by 52 weeks per year.


Secondary Outcome Measures:
  • Percentage of Participants With Objective Response [ Time Frame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) ] [ Designated as safety issue: No ]
    Objective Response Rate (ORR)=participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST,Version 1.0) based on third party independent imaging review laboratory assessment. A CR was defined as the disappearance of all target lesions that persisted on repeat imaging study at least 4 weeks after initial documentation of response. A PR was defined as a ≥30% decrease in sum of longest dimensions of target lesions taking as a reference the baseline sum longest dimensions.

  • Time to Tumor Progression (TTP) [ Time Frame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) ] [ Designated as safety issue: No ]
    TTP was defined as the time from date of randomization to first documentation of PD based on third party independent imaging review laboratory assessment. TTP was calculated as (first event date minus randomization date plus 1) divided by 7.02.

  • Duration of Response (DR) [ Time Frame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) ] [ Designated as safety issue: No ]
    DR was defined as time from first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of PD or death on-study due to any cause, whichever occurred first. DR was 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: From randomization until death (up to Month 17) ] [ Designated as safety issue: No ]
    OS was defined as time from date of randomization to date of death due to any cause. OS was calculated as (date of death minus date of randomization plus 1) divided by 30.4. For participants still alive at the time of analysis, OS time was censored on last date that participants were known to be alive.

  • Percentage of Participants Surviving at 1 Year [ Time Frame: From randomization until death (up until Month 17) ] [ Designated as safety issue: No ]
    Percentage of participants alive at 1 year after date of first administration of study medication.

  • Area Under the Curve From Time Zero to 24 Hours [AUC(0-24)] of Erlotinib [ Time Frame: Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose ] [ Designated as safety issue: No ]
    AUC0-24=Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours (0-24) of erlotinib

  • AUC(0-24) of Sunitinib [ Time Frame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, and 24 hours postdose ] [ Designated as safety issue: No ]
    AUC0-24=Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours (0-24) of sunitinib

  • AUC(0-24) of SU-012662 (Metabolite of Sunitinib) [ Time Frame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, and 24 hours postdose ] [ Designated as safety issue: No ]
    AUC0-24=Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours (0-24) of SU-012662 (metabolite of sunitinib)

  • AUC(0-24) of Total Drug (Sunitinib + SU-012662) [ Time Frame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, and 24 hours postdose ] [ Designated as safety issue: No ]
    AUC0-24=Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours (0-24) of total drug (sunitinib + SU-012662)

  • Maximum Observed Plasma Concentration (Cmax) of Erlotinib [ Time Frame: Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose ] [ Designated as safety issue: No ]
  • Cmax of Sunitinib [ Time Frame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose ] [ Designated as safety issue: No ]
  • Cmax of SU-012662 (Metabolite of Sunitinib) [ Time Frame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose ] [ Designated as safety issue: No ]
  • Cmax of Total Drug (Sunitinib + SU-012662) [ Time Frame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) for Erlotinib [ Time Frame: Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose; predose on Days 22 and 23 (Cycle 1) ] [ Designated as safety issue: No ]
    AUC (0-inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf) for erlotinib. It is obtained from AUC from time zero (pre-dose) to last quantifiable concentration(AUC[0-t]) plus AUC from time last quantifiable concentration extrapolated infinite time (AUC[t-inf])

  • AUC(0-inf) for Sunitinib [ Time Frame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose; predose on Days 15, 16, and 17 (Cycle 1) ] [ Designated as safety issue: No ]
    AUC (0 - inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf) for sunitinib. It is obtained from AUC(0-t) plus AUC(t-inf)

  • AUC(0-inf) for SU-012662 (Metabolite of Sunitinib) [ Time Frame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose; predose on Days 15, 16, and 17 (Cycle 1) ] [ Designated as safety issue: No ]
    AUC(0-inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf) for SU-012662 (metabolite of sunitinib). It is obtained from AUC(0-t) plus AUC(t-inf)

  • AUC(0-inf) for Total Drug (Sunitinib + SU-012662) [ Time Frame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose; predose on Days 15, 16, and 17 (Cycle 1) ] [ Designated as safety issue: No ]
    AUC(0-inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf) for total drug (sunitinib + SU-012662). It is obtained from AUC(0-t) plus AUC(t-inf)

  • Plasma Decay Half-life (t1/2) of Erlotinib [ Time Frame: Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Plasma Decay Half-life (t1/2) of Sunitinib [ Time Frame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Erlotinib Clearance at Steady State After Oral Administration (CL/F) [ Time Frame: Day 15 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose ] [ Designated as safety issue: No ]
  • Sunitinib Clearance at Steady State After Oral Administration (CL/F) [ Time Frame: Day 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) for Erlotinib [ Time Frame: Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose ] [ Designated as safety issue: No ]
  • Tmax for Sunitinib [ Time Frame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose ] [ Designated as safety issue: No ]
  • Tmax for SU-012662 (Metabolite of Sunitinib) [ Time Frame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose ] [ Designated as safety issue: No ]
  • Tmax for Total Drug (Sunitinib + SU-012662) [ Time Frame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose ] [ Designated as safety issue: No ]
  • Dose-Corrected Observed Plasma Trough Concentrations (Ctrough) for Erlotinib on Day 1 of Cycles 3-13 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) [ Time Frame: predose Day 1 (Cycles 3-13); predose Day 1 (Cycles 1-18) ] [ Designated as safety issue: No ]
    Ctrough = plasma concentration of erlotinib prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original and Amended Lead-In (Arms A and B) Cohorts predose on Day 1 (Cycles 3-13) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18.

  • Dose-Corrected Ctrough for Erlotinib on Day 15 Cycle 1 (Original), Day 1 of Cycle 3 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) [ Time Frame: predose Day 15 (Cycle1); predose Day 1 (Cycle 3); predose Day 1 (Cycles 1-18) ] [ Designated as safety issue: No ]
    Ctrough = plasma concentration of erlotinib prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original Cohort predose on Day 15 (Cycle 1, Time Zero) and Day 1 (Cycle 3), in the Amended Lead-In Cohort (Arms A and B) predose on Day 1 (Cycle 3) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18.

  • Dose-Corrected Ctrough for Sunitinib on Day 1 of Cycles 3-13 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) [ Time Frame: predose Day 1 (Cycles 3-13); predose Day 1 (Cycles 1-18) ] [ Designated as safety issue: No ]
    Ctrough = plasma concentration of sunitinib prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original and Amended Lead-In (Arms A and B) Cohorts predose on Day 1 (Cycles 3-13) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18.

  • Dose-Corrected Ctrough for Sunitinib on Day 15 Cycle 1 (Original), Day 1 of Cycle 3 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) [ Time Frame: predose Day 15 (Cycle 1) and Day 1 (Cycle 3); predose Day 1 (Cycle 3); predose Day 1 (Cycles 1-18) ] [ Designated as safety issue: No ]
    Ctrough = plasma concentration of sunitinib prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original Cohort predose on Day 15 (Cycle 1, Time Zero) and Day 1 (Cycle 3), in the Amended Lead-In Cohort (Arms A and B) predose on Day 1 (Cycle 3) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18.

  • Dose-Corrected Ctrough for SU-012662 (Metabolite of Sunitinib) on Day 1 of Cycles 3-13 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) [ Time Frame: predose Day 1 (Cycles 3-13); predose Day 1 (Cycles 1-18) ] [ Designated as safety issue: No ]
    Ctrough = plasma concentration of SU-012662 prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original and Amended Lead-In (Arms A and B) Cohorts predose on Day 1 (Cycles 3-13) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18.

  • Dose-Corrected Ctrough for SU-012662 (Metabolite of Sunitinib) on Day 15 Cycle 1 (Original), Day 1 of Cycle 3 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) [ Time Frame: predose Day 15 (Cycle 1) and Day 1 (Cycle 3); predose Day 1 (Cycle 3); predose Day 1 (Cycles 1-18) ] [ Designated as safety issue: No ]
    Ctrough = plasma concentration of SU-012662 prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original Cohort predose on Day 15 (Cycle 1, Time Zero) and Day 1 (Cycle 3), in the Amended Lead-In Cohort (Arms A and B) predose on Day 1 (Cycle 3) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18.

  • Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression by Immunohistochemistry (IHC) Using 0 Percent [%] Cutoff [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Percentage of participants with EGFR expression by IHC using a 0% cutoff; Reported as positive, negative, or unmeasured (where positive was greater than 0% of cells demonstrating membranous staining for EGFR). Correlative analysis of EGFR expression was conducted using tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable.

  • PFS in Subgroups That Were Defined by EGFR Expression (Using 0% Cutoff) [ Time Frame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) ] [ Designated as safety issue: No ]
    PFS defined as time in weeks from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in the following subgroups: positive, negative, or unmeasured EGFR expression. EGFR expression was analyzed using a 0% cutoff where positive was greater than 0% of cells demonstrating membranous staining for EGFR. PFS calculated as (first event date minus randomization date plus 1) divided by 7.02.

  • Percentage of Participants With EGFR Expression by IHC (Using 10% Cutoff) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Percentage of participants with EGFR Expression by IHC using a 10% cutoff; Reported as positive (positive values were defined as being greater than 10% of cells demonstrating membranous staining for EGFR), negative, or unmeasured. Correlative analysis of EGFR expression was conducted using tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable.

  • PFS in Subgroups That Were Defined by EGFR Expression (Using 10% Cutoff) [ Time Frame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) ] [ Designated as safety issue: No ]
    PFS defined as time in weeks from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in the following subgroups: positive, negative, or unmeasured EGFR expression. EGFR expression was analyzed using a 10% cutoff where positive was greater than 10% of cells demonstrating membranous staining for EGFR. PFS calculated as (first event date minus randomization date plus 1) divided by 7.02.

  • Percentage of Participants With EGFR Gene Copy Number Increase [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The number of copies corresponding to exon 19 of the EGFR gene was determined by real-time quantitative polymerase chain reaction (PCR). The percentage of participants with EGFR Gene Copy Number Increase (defined as greater than 4 copies) was determined using deoxyribonucleic acid (DNA) from tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable. Reported as yes, no or unmeasured.

  • PFS in Subgroups That Were Defined by EGFR Gene Copy Number Increase [ Time Frame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) ] [ Designated as safety issue: No ]
    PFS, defined as time from date of randomization to the date of the first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by EGFR gene copy number increase (reported as yes, no, or unmeasured). The number of copies corresponding to exon 19 of the EGFR gene was determined and an increase was defined as greater than 4 copies. PFS was calculated as (first event date minus randomization date plus 1)/7.02.

  • Percentage of Participants With EGFR Gene Amplification [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The percentage of participants with EGFR gene amplification (defined as greater than 15) was determined and reported as yes, no, or unmeasured. Correlative analysis of EGFR gene amplification was conducted using tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable.

  • PFS in Subgroups That Were Defined by EGFR Gene Amplification [ Time Frame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) ] [ Designated as safety issue: No ]
    PFS, defined as time from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by EGFR gene amplification (defined as greater than 15) and reported as no or unmeasured. PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02.

  • Percentage of Participants With EGFR Gene Mutation [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Mutations in exons 18 through 21 of the EGFR gene were analyzed by high-performance liquid chromatography using DNA from tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable. The percentage of participants with EGFR mutations categorized as mutated, wild type or indeterminate was reported.

  • PFS in Subgroups That Were Defined by EGFR Gene Mutation [ Time Frame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) ] [ Designated as safety issue: No ]
    PFS, defined as time from date of randomization to date of first documentation of PD or to death on-study due to any cause, whichever occurred first, in subgroups that were defined by EGFR gene mutation (reported as mutated, wild type, or indeterminate). PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02.

  • Percentage of Participants With KRAS (V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog) Gene Mutations [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Mutations in exons 2-3 of the KRAS gene (including codons 12, 13, and 61) were analyzed by high-performance liquid chromatography using DNA from tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable. The percentage of participants with KRAS mutations categorized as mutated, wild type or indeterminate was reported.

  • PFS in Subgroups That Were Defined by KRAS Gene Mutation [ Time Frame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) ] [ Designated as safety issue: No ]
    PFS, defined as time from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by KRAS gene mutation (reported as mutated, wild type, or indeterminate). PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02.

  • Percentage of Participants With Germline Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Polymorphisms [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Blood samples were collected at baseline for multiplex reverse transcription (RT) analysis of genes expressing proteins that are targets of sunitinib or involved in angiogenesis or tumor growth to determine expression levels. Percentage of participants with germline VEGFR2 single nucleotide polymorphisms (SNPs) was reported for the following genotype frequencies: homozygous C alleles (C/C), T alleles (T/T), G alleles (G/G), or A alleles (A/A), and the following heterozygous genotypes C/T, G/T, T/A, and G/A.

  • PFS in Subgroups That Were Defined by Germline VEGFR2 Polymorphisms [ Time Frame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) ] [ Designated as safety issue: No ]
    PFS, defined as time from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by VEGFR2 polymorphisms. PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02.

  • Overall Survival (OS) in Subgroups That Were Defined by Germline VEGFR2 Polymorphisms [ Time Frame: From randomization until death (up to Month 17) ] [ Designated as safety issue: No ]
    OS, defined as time from date of randomization to date of death due to any cause, in subgroups that were defined by VEGFR2 polymorphisms. OS was calculated as (date of death minus date of randomization plus 1) divided by 30.4.

  • Percentage of Participants With Germline Platelet-derived Growth Factor Receptor Beta (PDGFRB) Polymorphisms [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Blood samples were collected at baseline for multiplex RT analysis of genes expressing proteins that are targets of sunitinib or involved in angiogenesis or tumor growth to determine expression levels. Percentage of participants with germline PDGFRB SNPs was reported for the following genotype frequencies: homozygous C alleles (C/C), T alleles (T/T), G alleles (G/G), or A alleles (A/A), and the following heterozygous genotypes C/T, A/T, A/G, T/C, T/G, G/C, C/A and G/A.

  • PFS in Subgroups That Were Defined by Germline PDGFRB Polymorphisms [ Time Frame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) ] [ Designated as safety issue: No ]
    PFS, defined as time from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by PDGFRB polymorphisms. PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02.

  • OS in Subgroups That Were Defined by Germline PDGFRB Polymorphisms [ Time Frame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) ] [ Designated as safety issue: No ]
    OS, defined as time from date of randomization to date of death due to any cause, in subgroups that were defined by PDGFRB polymorphisms. OS was calculated as (date of death minus date of randomization plus 1) divided by 30.4.

  • Percentage of Participants by Tumor VEGFR Mutation [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Percentage of participants with VEGFR mutations in DNA from tumor samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable.

  • Correlation of Polymorphisms in Stem Cell Factor Receptor (c-Kit), FMS-like Tyrosine Kinase 3 Receptor (FLT-3), and c-FMS With Blood Counts [ Time Frame: Baseline (Day 1, Cycle 1) ] [ Designated as safety issue: No ]
    A blood sample (6 mL) was collected before on-study treatment and was used to isolate DNA. These samples were not anonymized. Correlation was investigated by the percentage of participants with anemia (based on hemoglobin count), neutropenia (based on neutrophil count) and thrombocytopenia (based on platelet count) endpoints and genetic variation as measured by c-KIT, FLT-3, and c-FMS was to be analyzed.

  • Percentage of Participants by Ribonucleic Acid (RNA) Expression Profile [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Includes colony-stimulating factor 1 receptor (CSF-1R), PDGFRalpha, PDGFRbeta, vascular endothelial growth factor (VEGF), VEGF C (VEGF-C), VEGF receptor 1 (VEGFR1), VEGF receptor 2 (VEGFR2), VEGF receptor 3 (VEGFR3), fibroblast growth factor (FGF), FLT-3, KIT (stem cell factor receptor), and RET (rearranged during transfection). Correlative analysis was conducted using tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable.

  • PFS in Subgroups That Were Defined by RNA Expression Profile [ Time Frame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) ] [ Designated as safety issue: No ]
    PFS, defined as time from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by RNA Gene expression (CSF-1R, PDGFRalpha, PDGFRbeta, VEGF, VEGF-C, VEGFR1, VEGFR2, VEGFR3, FGF, FLT-3, KIT, and RET). PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02.

  • Health Related Quality of Life (HRQoL) and Lung Cancer Related Symptoms as Assessed With European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) Score [ Time Frame: Baseline (Cycle [C] 1, Day [D] 1) to Cycle 18, Day 1 ] [ Designated as safety issue: No ]
    EORTC QLQ-C30: self-administered questionnaire assessing global health status/quality of life (QoL), functional domains (physical, role, cognitive, emotional, and social), symptom scales/items (fatigue, pain, nausea and vomiting, dyspnea, insomnia, loss of appetite, constipation, and diarrhea), and financial difficulties. Recall period: past week; response range: not at all (1) to very much (4); global/QoL range: very poor (1) to excellent (7). Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.

  • EORTC-QLQ-C30 Lung Cancer Module (LC13) Score [ Time Frame: Baseline (Cycle 1 [Day 1]) to Cycle 18 (Day 1) ] [ Designated as safety issue: No ]
    The EORTC-QLQ-C30 LC13 is a self-administered questionnaire assessing specific lung cancer disease related symptoms (dyspnea, coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in the chest, arm/shoulder or other parts of the body). Recall period: past week; response range: not at all (1) to very much (4). Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.

  • Number of Participants With Blood Pressure (BP) Greater Than 150/100 Millimeters of Mercury (mmHg) [ Time Frame: Randomization up until Month 17 ] [ Designated as safety issue: No ]
    Systolic/diastolic BP measured in triplicate (separated by approximately 2 minutes [min]) using validated electronic device (same device for all measurements), recorded to nearest mmHg. Dominant arm used (same one each time) with appropriate cuff size encircling at least 80% of arm. BP measured after 5 min rest and before invasive procedures, while seated in a chair with back supported, arms bared, supported at heart level. No smoking or caffeine use allowed during 30 min before measurement. Number of participants with systolic BP >150 mmHg/diastolic BP >100 mmHg at any timepoint postbaseline.

  • Number of Participants With BP Greater Than 200/110 mmHg [ Time Frame: Randomization up until Month 17 ] [ Designated as safety issue: No ]
    Systolic/diastolic BP measured in triplicate (separated by approximately 2 minutes [min]) using validated electronic device (same device for all measurements), recorded to nearest mmHg. Dominant arm used (same one each time) with appropriate cuff size encircling at least 80% of arm. BP measured after 5 min rest and before invasive procedures, while seated in a chair with back supported, arms bared, supported at heart level. No smoking or caffeine use allowed during 30 min before measurement. Number of participants with systolic BP >150 mmHg/diastolic BP >100 mmHg at any timepoint postbaseline.

  • Number of Participants on Anti-hypertensive Medications [ Time Frame: Randomization to Day 28 of Cycle 18 ] [ Designated as safety issue: No ]
    Number of participants with BP greater than 150/100 mmHg or 200/110 mmHg who were treated with anti-hypertensive medications.

  • Plasma Concentration of VEGF-C at Baseline [ Time Frame: Baseline (Cycle 1, Day 1) ] [ Designated as safety issue: No ]
  • Plasma Concentration of Soluble VEGFR-2 at Baseline [ Time Frame: Baseline (Cycle 1, Day 1) ] [ Designated as safety issue: No ]
  • Plasma Concentration of Soluble VEGFR-3 at Baseline [ Time Frame: Baseline (Cycle 1, Day 1) ] [ Designated as safety issue: No ]
  • Plasma Concentration of Soluble KIT (sKIT) at Baseline [ Time Frame: Baseline (Cycle 1, Day 1) ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • VEGF-C Ratio to Baseline at Each Timepoint [ Time Frame: Baseline to Cycle 2 (Day 1) and Cycle 3 (Day 1) ] [ Designated as safety issue: No ]
    Plasma VEGF-C concentration at each time point divided by VEGF-C concentration at baseline (ratio to baseline)

  • VEGFR-2 Ratio to Baseline at Each Timepoint [ Time Frame: Baseline to Cycle 2 (Day 1) and Cycle 3 (Day 1) ] [ Designated as safety issue: No ]
    Plasma VEGFR-2 concentration at each time point divided by VEGFR-2 concentration at baseline (ratio to baseline)

  • VEGFR-3 Ratio to Baseline at Each Timepoint [ Time Frame: Baseline to Cycle 2 (Day 1) and Cycle 3 (Day 1) ] [ Designated as safety issue: No ]
    Plasma VEGFR-3 concentration at each time point divided by VEGFR-3 concentration at baseline (ratio to baseline)

  • sKIT Ratio to Baseline at Each Timepoint [ Time Frame: Baseline to Cycle 2 (Day 1) and Cycle 3 (Day 1) ] [ Designated as safety issue: No ]
    Plasma sKIT concentration at each time point divided by sKIT concentration at baseline (ratio to baseline)


Enrollment: 162
Study Start Date: June 2006
Study Completion Date: January 2012
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: erlotinib
erlotinib 150 mg daily by tablets in a continuous regimen, until progression or unacceptable toxicity
Drug: sunitinib
Sunitinib 37.5 mg daily by oral capsule in a continuous regimen plus erlotinib 150 mg daily by tablets in a continuous regimen, until progression or unacceptable toxicity
Other Name: Sutent
Active Comparator: B Drug: erlotinib
erlotinib 150 mg daily by tablets in a continuous regimen, until progression or unacceptable toxicity
Drug: placebo
Placebo daily by oral capsule in a continuous regimen plus erlotinib 150 mg daily by tablets in a continuous regimen, until progression or unacceptable toxicity

  Eligibility

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

Inclusion Criteria:

  • Patients with locally advanced/metastatic non-small cell lung cancer
  • Prior treatment with no more than 2 chemotherapy regimens including a platinum-based regimen

Exclusion Criteria:

  • Prior treatment with any receptor tyrosine kinase inhibitors, Vascular endothelial growth factor (VEGF) inhibitors or other angiogenic inhibitors
  • History of or known brain metastases
  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: NCT00265317

  Show 32 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00265317     History of Changes
Other Study ID Numbers: A6181058
Study First Received: December 12, 2005
Results First Received: January 21, 2011
Last Updated: January 31, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Non-small cell lung cancer
sunitinib
erlotinib
Phase 2

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Erlotinib
Sunitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014