Clinical trial NCT00265317: A Study In Patients With Non-Small Cell Lung Cancer Testing If Erlotinib Plus SU011248 (Sunitinib) Is Better Than Erlotinib Alone
Official title: Randomized, Double-Blind, Phase 2 Study Of Erlotinib With Or Without SU011248 In The Treatment Of Metastatic Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Non-small cell lung cancer
sunitinib
erlotinib
Phase 2
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2005-12-14
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)
Secondary outcomes:
measure: Percentage of Participants With Objective Response
timeFrame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)
measure: Time to Tumor Progression (TTP)
timeFrame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)
measure: Duration of Response (DR)
timeFrame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)
measure: Overall Survival (OS)
timeFrame: From randomization until death (up to Month 17)
measure: Percentage of Participants Surviving at 1 Year
timeFrame: From randomization until death (up until Month 17)
measure: Area Under the Curve From Time Zero to 24 Hours [AUC(0-24)] of Erlotinib
timeFrame: Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose
measure: AUC(0-24) of Sunitinib
timeFrame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, and 24 hours postdose
measure: AUC(0-24) of SU-012662 (Metabolite of Sunitinib)
timeFrame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, and 24 hours postdose
measure: AUC(0-24) of Total Drug (Sunitinib + SU-012662)
timeFrame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, and 24 hours postdose
measure: Maximum Observed Plasma Concentration (Cmax) of Erlotinib
timeFrame: Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose
measure: Cmax of Sunitinib
timeFrame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose
measure: Cmax of SU-012662 (Metabolite of Sunitinib)
timeFrame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose
measure: Cmax of Total Drug (Sunitinib + SU-012662)
timeFrame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) for Erlotinib
timeFrame: 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)
measure: AUC(0-inf) for Sunitinib
timeFrame: 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)
measure: AUC(0-inf) for SU-012662 (Metabolite of Sunitinib)
timeFrame: 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)
measure: AUC(0-inf) for Total Drug (Sunitinib + SU-012662)
timeFrame: 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)
measure: Plasma Decay Half-life (t1/2) of Erlotinib
timeFrame: Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose
measure: Plasma Decay Half-life (t1/2) of Sunitinib
timeFrame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose
measure: Erlotinib Clearance at Steady State After Oral Administration (CL/F)
timeFrame: Day 15 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose
measure: Sunitinib Clearance at Steady State After Oral Administration (CL/F)
timeFrame: Day 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Erlotinib
timeFrame: Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose
measure: Tmax for Sunitinib
timeFrame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose
measure: Tmax for SU-012662 (Metabolite of Sunitinib)
timeFrame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose
measure: Tmax for Total Drug (Sunitinib + SU-012662)
timeFrame: Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose
measure: 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)
timeFrame: predose Day 1 (Cycles 3-13); predose Day 1 (Cycles 1-18)
measure: 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)
timeFrame: predose Day 15 (Cycle1); predose Day 1 (Cycle 3); predose Day 1 (Cycles 1-18)
measure: 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)
timeFrame: predose Day 1 (Cycles 3-13); predose Day 1 (Cycles 1-18)
measure: 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)
timeFrame: predose Day 15 (Cycle 1) and Day 1 (Cycle 3); predose Day 1 (Cycle 3); predose Day 1 (Cycles 1-18)
measure: 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)
timeFrame: predose Day 1 (Cycles 3-13); predose Day 1 (Cycles 1-18)
measure: 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)
timeFrame: predose Day 15 (Cycle 1) and Day 1 (Cycle 3); predose Day 1 (Cycle 3); predose Day 1 (Cycles 1-18)
measure: Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression by Immunohistochemistry (IHC) Using 0 Percent [%] Cutoff
timeFrame: Baseline
measure: PFS in Subgroups That Were Defined by EGFR Expression (Using 0% Cutoff)
timeFrame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)
measure: Percentage of Participants With EGFR Expression by IHC (Using 10% Cutoff)
timeFrame: Baseline
measure: PFS in Subgroups That Were Defined by EGFR Expression (Using 10% Cutoff)
timeFrame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)
measure: Percentage of Participants With EGFR Gene Copy Number Increase
timeFrame: Baseline
measure: PFS in Subgroups That Were Defined by EGFR Gene Copy Number Increase
timeFrame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)
measure: Percentage of Participants With EGFR Gene Amplification
timeFrame: Baseline
measure: PFS in Subgroups That Were Defined by EGFR Gene Amplification
timeFrame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)
measure: Percentage of Participants With EGFR Gene Mutation
timeFrame: Baseline
measure: PFS in Subgroups That Were Defined by EGFR Gene Mutation
timeFrame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)
measure: Percentage of Participants With KRAS (V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog) Gene Mutations
timeFrame: Baseline
measure: PFS in Subgroups That Were Defined by KRAS Gene Mutation
timeFrame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)
measure: Percentage of Participants With Germline Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Polymorphisms
timeFrame: Baseline
measure: PFS in Subgroups That Were Defined by Germline VEGFR2 Polymorphisms
timeFrame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)
measure: Overall Survival (OS) in Subgroups That Were Defined by Germline VEGFR2 Polymorphisms
timeFrame: From randomization until death (up to Month 17)
measure: Percentage of Participants With Germline Platelet-derived Growth Factor Receptor Beta (PDGFRB) Polymorphisms
timeFrame: Baseline
measure: PFS in Subgroups That Were Defined by Germline PDGFRB Polymorphisms
timeFrame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)
measure: OS in Subgroups That Were Defined by Germline PDGFRB Polymorphisms
timeFrame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)
measure: Percentage of Participants by Tumor VEGFR Mutation
timeFrame: Baseline
measure: Correlation of Polymorphisms in Stem Cell Factor Receptor (c-Kit), FMS-like Tyrosine Kinase 3 Receptor (FLT-3), and c-FMS With Blood Counts
timeFrame: Baseline (Day 1, Cycle 1)
measure: Percentage of Participants by Ribonucleic Acid (RNA) Expression Profile
timeFrame: Baseline
measure: PFS in Subgroups That Were Defined by RNA Expression Profile
timeFrame: From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)
measure: 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
timeFrame: Baseline (Cycle [C] 1, Day [D] 1) to Cycle 18, Day 1
measure: EORTC-QLQ-C30 Lung Cancer Module (LC13) Score
timeFrame: Baseline (Cycle 1 [Day 1]) to Cycle 18 (Day 1)
measure: Number of Participants With Blood Pressure (BP) Greater Than 150/100 Millimeters of Mercury (mmHg)
timeFrame: Randomization up until Month 17
measure: Number of Participants With BP Greater Than 200/110 mmHg
timeFrame: Randomization up until Month 17
measure: Number of Participants on Anti-hypertensive Medications
timeFrame: Randomization to Day 28 of Cycle 18
measure: Plasma Concentration of VEGF-C at Baseline
timeFrame: Baseline (Cycle 1, Day 1)
measure: Plasma Concentration of Soluble VEGFR-2 at Baseline
timeFrame: Baseline (Cycle 1, Day 1)
measure: Plasma Concentration of Soluble VEGFR-3 at Baseline
timeFrame: Baseline (Cycle 1, Day 1)
measure: Plasma Concentration of Soluble KIT (sKIT) at Baseline
timeFrame: Baseline (Cycle 1, Day 1)
Other outcomes:
measure: VEGF-C Ratio to Baseline at Each Timepoint
timeFrame: Baseline to Cycle 2 (Day 1) and Cycle 3 (Day 1)
measure: VEGFR-2 Ratio to Baseline at Each Timepoint
timeFrame: Baseline to Cycle 2 (Day 1) and Cycle 3 (Day 1)
measure: VEGFR-3 Ratio to Baseline at Each Timepoint
timeFrame: Baseline to Cycle 2 (Day 1) and Cycle 3 (Day 1)
measure: sKIT Ratio to Baseline at Each Timepoint
timeFrame: Baseline to Cycle 2 (Day 1) and Cycle 3 (Day 1)
Locations:
city: Birmingham
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Mobile
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Antioch
country: United States
facility: Pfizer Investigational Site
state: California
city: Palm Springs
country: United States
facility: Pfizer Investigational Site
state: California
city: Pleasant Hill
country: United States
facility: Pfizer Investigational Site
state: California
city: San Leandro
country: United States
facility: Pfizer Investigational Site
state: California
city: Chicago
country: United States
facility: Pfizer Investigational Site
state: Illinois
city: Creve Coeur
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: St. Peters
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: Chapel Hill
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Clinton
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Goldsboro
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Wilson
country: United States
facility: Pfizer Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: Pfizer Investigational Site
state: Ohio
city: Houston
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Edmonton
country: Canada
facility: Pfizer Investigational Site
state: Alberta
city: Hamilton
country: Canada
facility: Pfizer Investigational Site
state: Ontario
city: Budapest
country: Hungary
facility: Pfizer Investigational Site
city: Torokbalint
country: Hungary
facility: Pfizer Investigational Site
city: Genova
country: Italy
facility: Pfizer Investigational Site
city: Monteforte Irpino, AV
country: Italy
facility: Pfizer Investigational Site
city: Amsterdam
country: Netherlands
facility: Pfizer Investigational Site
city: Groningen
country: Netherlands
facility: Pfizer Investigational Site
city: Bydgoszcz
country: Poland
facility: Pfizer Investigational Site
city: Gdansk
country: Poland
facility: Pfizer Investigational Site
city: Cluj-Napoca
country: Romania
facility: Pfizer Investigational Site
state: Cluj
city: Bucuresti
country: Romania
facility: Pfizer Investigational Site
state: Sector 2
city: Bucuresti
country: Romania
facility: Pfizer Investigational Site
city: Santander
country: Spain
facility: Pfizer Investigational Site
state: Cantabria
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Groen HJ, Socinski MA, Grossi F, Juhasz E, Gridelli C, Baas P, Butts CA, Chmielowska E, Usari T, Selaru P, Harmon C, Williams JA, Gao F, Tye L, Chao RC, Blumenschein GR Jr. A randomized, double-blind, phase II study of erlotinib with or without sunitinib for the second-line treatment of metastatic non-small-cell lung cancer (NSCLC). Ann Oncol. 2013 Sep;24(9):2382-9. doi: 10.1093/annonc/mdt212. Epub 2013 Jun 20.