Randomized, Double-Blind, Phase 2 Study Of Erlotinib With Or Without SU011248 In The Treatment Of Metastatic Non-Small Cell Lung Cancer

Pfizer1 site in 1 country162 target enrollmentJune 2006

ConditionsCarcinoma, Non-Small-Cell Lung

Interventionserlotinib sunitinib placebo

Drugserlotinib sunitinib placebo

Overview

Phase: Phase 2
Intervention: erlotinib
Conditions: Carcinoma, Non-Small-Cell Lung
Sponsor: Pfizer
Enrollment: 162
Locations: 1
Primary Endpoint: Progression-Free Survival (PFS)
Status: Completed
Last Updated: 13 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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

Registry

clinicaltrials.gov

Start Date

June 2006

End Date

January 2012

Last Updated

13 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Pfizer

Responsible Party

Sponsor

Eligibility 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

Arms & Interventions

A

Intervention: erlotinib

A

Intervention: sunitinib

B

Intervention: erlotinib

B

Intervention: placebo

Outcomes

Primary Outcomes

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)

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 Outcomes

Erlotinib Clearance at Steady State After Oral Administration (CL/F)(Day 15 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose)
Plasma Decay Half-life (t1/2) of Erlotinib(Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose)
Plasma Decay Half-life (t1/2) of Sunitinib(Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose)
Percentage of Participants With Objective Response(From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17))
Time to Tumor Progression (TTP)(From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17))
Duration of Response (DR)(From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17))
Overall Survival (OS)(From randomization until death (up to Month 17))
Percentage of Participants Surviving at 1 Year(From randomization until death (up until Month 17))
Area Under the Curve From Time Zero to 24 Hours [AUC(0-24)] of Erlotinib(Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose)
AUC(0-24) of Sunitinib(Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, and 24 hours postdose)
AUC(0-24) of SU-012662 (Metabolite of Sunitinib)(Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, and 24 hours postdose)
AUC(0-24) of Total Drug (Sunitinib + SU-012662)(Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, and 24 hours postdose)
Maximum Observed Plasma Concentration (Cmax) of Erlotinib(Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose)
Cmax of Sunitinib(Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose)
Cmax of SU-012662 (Metabolite of Sunitinib)(Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose)
Cmax of Total Drug (Sunitinib + SU-012662)(Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose)
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) for Erlotinib(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))
AUC(0-inf) for Sunitinib(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))
AUC(0-inf) for SU-012662 (Metabolite of Sunitinib)(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))
AUC(0-inf) for Total Drug (Sunitinib + SU-012662)(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))
Sunitinib Clearance at Steady State After Oral Administration (CL/F)(Day 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose)
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Erlotinib(Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose)
Tmax for Sunitinib(Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose)
Tmax for SU-012662 (Metabolite of Sunitinib)(Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose)
Tmax for Total Drug (Sunitinib + SU-012662)(Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose)
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)(predose Day 1 (Cycles 3-13); predose Day 1 (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)(predose Day 15 (Cycle1); predose Day 1 (Cycle 3); predose Day 1 (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)(predose Day 1 (Cycles 3-13); predose Day 1 (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)(predose Day 15 (Cycle 1) and Day 1 (Cycle 3); predose Day 1 (Cycle 3); predose Day 1 (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)(predose Day 1 (Cycles 3-13); predose Day 1 (Cycles 1-18))
Percentage of Participants With KRAS (V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog) Gene Mutations(Baseline)
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)(predose Day 15 (Cycle 1) and Day 1 (Cycle 3); predose Day 1 (Cycle 3); predose Day 1 (Cycles 1-18))
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression by Immunohistochemistry (IHC) Using 0 Percent [%] Cutoff(Baseline)
EORTC-QLQ-C30 Lung Cancer Module (LC13) Score(Baseline (Cycle 1 [Day 1]) to Cycle 18 (Day 1))
PFS in Subgroups That Were Defined by EGFR Expression (Using 0% Cutoff)(From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17))
Percentage of Participants With EGFR Expression by IHC (Using 10% Cutoff)(Baseline)
PFS in Subgroups That Were Defined by EGFR Expression (Using 10% Cutoff)(From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17))
Percentage of Participants With EGFR Gene Copy Number Increase(Baseline)
PFS in Subgroups That Were Defined by EGFR Gene Copy Number Increase(From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17))
Percentage of Participants With EGFR Gene Amplification(Baseline)
PFS in Subgroups That Were Defined by EGFR Gene Amplification(From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17))
Percentage of Participants With EGFR Gene Mutation(Baseline)
PFS in Subgroups That Were Defined by EGFR Gene Mutation(From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17))
PFS in Subgroups That Were Defined by KRAS Gene Mutation(From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17))
Percentage of Participants With Germline Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Polymorphisms(Baseline)
PFS in Subgroups That Were Defined by Germline VEGFR2 Polymorphisms(From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17))
Overall Survival (OS) in Subgroups That Were Defined by Germline VEGFR2 Polymorphisms(From randomization until death (up to Month 17))
Percentage of Participants With Germline Platelet-derived Growth Factor Receptor Beta (PDGFRB) Polymorphisms(Baseline)
PFS in Subgroups That Were Defined by Germline PDGFRB Polymorphisms(From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17))
OS in Subgroups That Were Defined by Germline PDGFRB Polymorphisms(From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17))
Percentage of Participants by Tumor VEGFR Mutation(Baseline)
Correlation of Polymorphisms in Stem Cell Factor Receptor (c-Kit), FMS-like Tyrosine Kinase 3 Receptor (FLT-3), and c-FMS With Blood Counts(Baseline (Day 1, Cycle 1))
Percentage of Participants by Ribonucleic Acid (RNA) Expression Profile(Baseline)
PFS in Subgroups That Were Defined by RNA Expression Profile(From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17))
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(Baseline (Cycle [C] 1, Day [D] 1) to Cycle 18, Day 1)
Number of Participants With Blood Pressure (BP) Greater Than 150/100 Millimeters of Mercury (mmHg)(Randomization up until Month 17)
Number of Participants With BP Greater Than 200/110 mmHg(Randomization up until Month 17)
Number of Participants on Anti-hypertensive Medications(Randomization to Day 28 of Cycle 18)
Plasma Concentration of VEGF-C at Baseline(Baseline (Cycle 1, Day 1))
Plasma Concentration of Soluble VEGFR-2 at Baseline(Baseline (Cycle 1, Day 1))
Plasma Concentration of Soluble VEGFR-3 at Baseline(Baseline (Cycle 1, Day 1))
Plasma Concentration of Soluble KIT (sKIT) at Baseline(Baseline (Cycle 1, Day 1))