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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01121575




Registration number
NCT01121575
Ethics application status
Date submitted
10/05/2010
Date registered
12/05/2010
Date last updated
28/10/2015

Titles & IDs
Public title
A Study Of Combined C- MET Inhibitor And PAN-HER Inhibitor (PF-02341066 And PF-00299804) In Patients With Non- Small Cell Lung Cancer
Scientific 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
Secondary ID [1] 0 0
A8081006
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PF-02341066
Treatment: Drugs - PF-00299804
Treatment: Drugs - PF-02341066
Treatment: Drugs - PF-00299804

Experimental: Arm 1 - PF-02341066 AND PF-00299804: Patients will be treated with combined cMET inhibitor (PF-02341066) and panHER inhibitor (PF-00299804).

Experimental: Arm 2 - PF-00299804 FOLLOWED BY COMBINED PF-02341066 AND PF-00299804: Patients will be treated with single agent panHER inhibitor (PF-00299804) until disease progression and then with the maximum tolerated combined dose of cMET inhibitor (PF-02341066) and panHER inhibitor (PF-00299804).


Treatment: Drugs: PF-02341066
Arm 1: The starting dose will be 200 mg by mouth, twice a day of PF 02341066 in tablet form The dose of each drug in the combination \[PF-02341066 and PF-00299804\] will be escalated or de-escalated until the maximum tolerated combined dose is reached. Patients will then be treated with the maximum tolerated combined dose.

Treatment: Drugs: PF-00299804
Arm 1: The starting dose will be 30 mg by mouth once a day of PF-0029804 in tablet form. The dose of each drug in the combination \[PF-02341066 and PF-00299804\] will be escalated or de-escalated until the maximum tolerated combined dose is reached. Patients will then be treated with the maximum tolerated combined dose.

Treatment: Drugs: PF-02341066
Arm 2: With progressive disease the maximum tolerated combined dose of PF-02341066 (given by mouth twice a day in tablet form) and PF-00299804 (given by mouth once a day in tablet form).

Treatment: Drugs: PF-00299804
Arm 2: The dose of 45 mg by mouth once a day of PF-00299804 in tablet form until progressive disease and then the maximum tolerated combined dose of PF-02341066 (given by mouth twice a day in tablet form) and PF-00299804 (given by mouth once a day in tablet form).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overview of Treatment-emergent All Causalities Adverse Events (AEs) in Escalation Phase
Timepoint [1] 0 0
Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)
Primary outcome [2] 0 0
Overview of Treatment-emergent All Causalities AEs in Expansion Phase
Timepoint [2] 0 0
Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)
Primary outcome [3] 0 0
Overview of Treatment-emergent, Treatment-related AEs in Escalation Phase
Timepoint [3] 0 0
Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)
Primary outcome [4] 0 0
Overview of Treatment-emergent, Treatment-related AEs in Expansion Phase
Timepoint [4] 0 0
Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)
Primary outcome [5] 0 0
Number of Participants With Dose Limiting Toxicities (DLTs) in Escalation Phase
Timepoint [5] 0 0
Cycle 1 (4 weeks)
Secondary outcome [1] 0 0
Number of Participants With Stable Disease and Stable Disease Duration in Escalation Phase
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Number of Participants With Stable Disease and Stable Disease Duration in Expansion Phase
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Number of Participants With Objective Response Rate (ORR) in Escalation Phase
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
Number of Participants With ORR in Expansion Phase
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Duration of Response for the Only Participant Shown Partial Response in Expansion Phase
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Progression Free Survival (PFS) in Escalation Phase
Timepoint [6] 0 0
From randomization to objective tumor progression or death (up to post treatment follow-up as 28-35 days after last dose of study treatment)
Secondary outcome [7] 0 0
Progression Free Survival (PFS) in Expansion Phase
Timepoint [7] 0 0
From randomization to objective tumor progression or death (up to post treatment follow-up as 28-35 days after last dose of study treatment)
Secondary outcome [8] 0 0
Expression Analysis of Tumor Biomarkers (HGF, EGFR, and c-Met ) at Baseline Using Immunohistochemistry (IHC) Method
Timepoint [8] 0 0
Baseline
Secondary outcome [9] 0 0
Expression Analysis of Tumor Biomarkers (EGFR, and c-Met) at Baseline Using Fluorescent in Situ Hybridization (FISH) Method
Timepoint [9] 0 0
Baseline
Secondary outcome [10] 0 0
Number of Participants With c-Met, HER2, EGFR Amplification and ALK Rearrangement at Baseline Using FISH Method
Timepoint [10] 0 0
Baseline
Secondary outcome [11] 0 0
Plasma Concentration of sMet by Study Visits
Timepoint [11] 0 0
At screening and Cycle 1 Day 1 (C1D1) (6 hours post dose), and C1D15, C2D1, C2D15 (all predose).
Secondary outcome [12] 0 0
Number of Participants With EGFR Mutation at Baseline
Timepoint [12] 0 0
Baseline
Secondary outcome [13] 0 0
Number of Participants With KRAS Mutation (GLY12CYS) at Baseline
Timepoint [13] 0 0
Baseline
Secondary outcome [14] 0 0
Number of Participants With PIK3CA Mutation at Baseline
Timepoint [14] 0 0
Baseline
Secondary outcome [15] 0 0
Number of Participants With ROS1 Gene Translocation at Baseline
Timepoint [15] 0 0
Baseline
Secondary outcome [16] 0 0
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)
Timepoint [16] 0 0
Cycle 1 (C1)/Day 1 (D1), C1D15
Secondary outcome [17] 0 0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Curve 10 (AUC10)
Timepoint [17] 0 0
C1D1, C1D15
Secondary outcome [18] 0 0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Maximum Plasma Concentration (Cmax)
Timepoint [18] 0 0
C1D1, C1D15
Secondary outcome [19] 0 0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Time of Last Quantifiable Concentration (Tlast)
Timepoint [19] 0 0
C1D1, C1D15
Secondary outcome [20] 0 0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase -Time to Maximum Plasma Concentration (Tmax)
Timepoint [20] 0 0
C1D1, C1D15
Secondary outcome [21] 0 0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUClast
Timepoint [21] 0 0
C1D1, C1D15
Secondary outcome [22] 0 0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUC24
Timepoint [22] 0 0
C1D1, C1D15
Secondary outcome [23] 0 0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Cmax
Timepoint [23] 0 0
C1D1, C1D15
Secondary outcome [24] 0 0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tlast
Timepoint [24] 0 0
C1D1, C1D15
Secondary outcome [25] 0 0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tmax
Timepoint [25] 0 0
C1D1, C1D15
Secondary outcome [26] 0 0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - AUClast
Timepoint [26] 0 0
Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
Secondary outcome [27] 0 0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - AUC10
Timepoint [27] 0 0
Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
Secondary outcome [28] 0 0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Cmin
Timepoint [28] 0 0
Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
Secondary outcome [29] 0 0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Cmax
Timepoint [29] 0 0
Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
Secondary outcome [30] 0 0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Tlast
Timepoint [30] 0 0
Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
Secondary outcome [31] 0 0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Tmax
Timepoint [31] 0 0
Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
Secondary outcome [32] 0 0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - AUClast
Timepoint [32] 0 0
Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
Secondary outcome [33] 0 0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - AUC24
Timepoint [33] 0 0
Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
Secondary outcome [34] 0 0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Cmin
Timepoint [34] 0 0
Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
Secondary outcome [35] 0 0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Cmax
Timepoint [35] 0 0
Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
Secondary outcome [36] 0 0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Tlast
Timepoint [36] 0 0
Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
Secondary outcome [37] 0 0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Tmax
Timepoint [37] 0 0
Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)

Eligibility
Key inclusion criteria
* advanced non small cell lung cancer (dose escalation phase)
* acquired resistance to erlotinib or gefitinib (expansion phase)
* mandatory entrance biopsy (expansion phase)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* interstitial lung disease
* unstable brain metastases
* leptomeningeal disease

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2014
Sample size
Target
Accrual to date
Final
70
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre, Division of Haematology and Medical Oncology - East Melbourne
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01121575
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01121575