Clinical trial NCT01121575: A Study Of Combined C- MET Inhibitor And PAN-HER Inhibitor (PF-02341066 And PF-00299804) In Patients With Non- Small Cell Lung Cancer
Official title: A Phase 1, Open-label, Dose Escalation Study To Evaluate Safety, Pharmacokinetics And Pharmacodynamics Of Combined Oral C-met/Alk Inhibitor (Pf-02341066) And Pan-her Inhibitor (Pf-00299804) In Patients With Advanced Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non Small Cell Lung Cancer
Keywords: Phase 1 acquired resistance to erlotinib or gefitinib cMET inhibitor EGFR inhibitor panHER inhibitor combination trial Crizotinib
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-05-12
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Lung cancer tumors become resistant to the first generation epidermal growth factor receptor (EGFR) inhibitors erlotinib or gefitinib by changing and increasing the activity of two cell signaling pathways: the cMET pathway and the EGFR pathway. Both resistance mechanisms can occur at the same time, in the same patient and even in the same tumor. This study combines a second generation EGFR inhibitor and a cMET inhibitor to block both these pathways in order to overcome resistance and treat this disease.


Eligibility criteria: Inclusion Criteria:

* advanced non small cell lung cancer (dose escalation phase)
* acquired resistance to erlotinib or gefitinib (expansion phase)
* mandatory entrance biopsy (expansion phase)

Exclusion Criteria:

* interstitial lung disease
* unstable brain metastases
* leptomeningeal disease

Primary outcomes:
measure: Overview of Treatment-emergent All Causalities Adverse Events (AEs) in Escalation Phase
timeFrame: Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)
measure: Overview of Treatment-emergent All Causalities AEs in Expansion Phase
timeFrame: Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)
measure: Overview of Treatment-emergent, Treatment-related AEs in Escalation Phase
timeFrame: Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)
measure: Overview of Treatment-emergent, Treatment-related AEs in Expansion Phase
timeFrame: Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)
measure: Number of Participants With Dose Limiting Toxicities (DLTs) in Escalation Phase
timeFrame: Cycle 1 (4 weeks)
Secondary outcomes:
measure: Number of Participants With Stable Disease and Stable Disease Duration in Escalation Phase
timeFrame: From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)
measure: Number of Participants With Stable Disease and Stable Disease Duration in Expansion Phase
timeFrame: From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)
measure: Number of Participants With Objective Response Rate (ORR) in Escalation Phase
timeFrame: From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)
measure: Number of Participants With ORR in Expansion Phase
timeFrame: From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)
measure: Duration of Response for the Only Participant Shown Partial Response in Expansion Phase
timeFrame: From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)
measure: Progression Free Survival (PFS) in Escalation Phase
timeFrame: From randomization to objective tumor progression or death (up to post treatment follow-up as 28-35 days after last dose of study treatment)
measure: Progression Free Survival (PFS) in Expansion Phase
timeFrame: From randomization to objective tumor progression or death (up to post treatment follow-up as 28-35 days after last dose of study treatment)
measure: Expression Analysis of Tumor Biomarkers (HGF, EGFR, and c-Met ) at Baseline Using Immunohistochemistry (IHC) Method
timeFrame: Baseline
measure: Expression Analysis of Tumor Biomarkers (EGFR, and c-Met) at Baseline Using Fluorescent in Situ Hybridization (FISH) Method
timeFrame: Baseline
measure: Number of Participants With c-Met, HER2, EGFR Amplification and ALK Rearrangement at Baseline Using FISH Method
timeFrame: Baseline
measure: Plasma Concentration of sMet by Study Visits
timeFrame: At screening and Cycle 1 Day 1 (C1D1) (6 hours post dose), and C1D15, C2D1, C2D15 (all predose).
measure: Number of Participants With EGFR Mutation at Baseline
timeFrame: Baseline
measure: Number of Participants With KRAS Mutation (GLY12CYS) at Baseline
timeFrame: Baseline
measure: Number of Participants With PIK3CA Mutation at Baseline
timeFrame: Baseline
measure: Number of Participants With ROS1 Gene Translocation at Baseline
timeFrame: Baseline
measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Concentration (AUClast)
timeFrame: Cycle 1 (C1)/Day 1 (D1), C1D15
measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Curve 10 (AUC10)
timeFrame: C1D1, C1D15
measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Maximum Plasma Concentration (Cmax)
timeFrame: C1D1, C1D15
measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Time of Last Quantifiable Concentration (Tlast)
timeFrame: C1D1, C1D15
measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase -Time to Maximum Plasma Concentration (Tmax)
timeFrame: C1D1, C1D15
measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUClast
timeFrame: C1D1, C1D15
measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUC24
timeFrame: C1D1, C1D15
measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Cmax
timeFrame: C1D1, C1D15
measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tlast
timeFrame: C1D1, C1D15
measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tmax
timeFrame: C1D1, C1D15
measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - AUClast
timeFrame: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - AUC10
timeFrame: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Cmin
timeFrame: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Cmax
timeFrame: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Tlast
timeFrame: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Tmax
timeFrame: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - AUClast
timeFrame: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - AUC24
timeFrame: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Cmin
timeFrame: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Cmax
timeFrame: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Tlast
timeFrame: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Tmax
timeFrame: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Clinical Trials Office University of Colorado Hospital (CTO)
state: Colorado
city: Aurora
country: United States
facility: DRUG SHIPMENT: University of Colorado Cancer Center
state: Colorado
city: Aurora
country: United States
facility: Rocky Mountain Lions Eye Institute
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Bethesda
country: United States
facility: CCR, National Cancer Institute
state: Maryland
city: Boston
country: United States
facility: Drug Shipment Only
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Drug Shipment Only
state: Massachusetts
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre, Division of Haematology and Medical Oncology
state: Victoria
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: