A Study Of Combined C- MET Inhibitor And PAN-HER Inhibitor (PF-02341066 And PF-00299804) In Patients With Non- Small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01121575
First received: May 10, 2010
Last updated: March 27, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention Phase
Non Small Cell Lung Cancer
Drug: PF-02341066
Drug: PF-00299804
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Overview of Treatment-emergent All Causalities Adverse Events (AEs) in Escalation Phase [ Time Frame: Up to Maximum of treatment duration + 28 days for each participant (could be 295 days) ] [ Designated as safety issue: Yes ]
    AE was any untoward medical occurrence with study drug/ device in a trial participant. Serious adverse event (SAE) was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.

  • Overview of Treatment-emergent All Causalities AEs in Expansion Phase [ Time Frame: Up to Maximum of treatment duration + 28 days for each participant (could be 295 days) ] [ Designated as safety issue: Yes ]
    AE was any untoward medical occurrence with study drug/ device in a trial participant. SAE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using NCI CTCAE v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.

  • Overview of Treatment-emergent, Treatment-related AEs in Escalation Phase [ Time Frame: Up to Maximum of treatment duration + 28 days for each participant (could be 295 days) ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. SAE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using NCI CTCAE v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.

  • Overview of Treatment-emergent, Treatment-related AEs in Expansion Phase [ Time Frame: Up to Maximum of treatment duration + 28 days for each participant (could be 295 days) ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. SAE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using NCI CTCAE v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.

  • Number of Participants With Dose Limiting Toxicities (DLTs) in Escalation Phase [ Time Frame: Cycle 1 (4 weeks) ] [ Designated as safety issue: Yes ]
    DLTs were those AEs which occurred in Cycle 1 of treatment in Dose Escalation Phase which may be attributed to study drug [combined Crizotinib (PF-02341066) plus Dacomitinib (PF-00299804)] without a clear alternative explanation and despite the use of adequate/maximal medical intervention as dictated by local institutional clinical practices or the judgment of the investigator. The following events were considered DLTs (using CTCAE version 4.02);1. Grade ≥4 hematologic events. 2. Grade ≥3 non-hematological events (except Grade 3/4 asymptomatic hypophosphatemia and Grade 3/4 hyperuricemia without signs and symptoms of gout). Nausea, vomiting or diarrhea had to have persisted at Grade 3 or 4 despite maximal medical therapy. Grade 3 hypertension will be considered a DLT only if the event is unmanageable by standard approved pharmacologic agents or if the symptomatic sequelae are identified despite appropriate medical intervention.


Secondary Outcome Measures:
  • Number of Participants With Stable Disease and Stable Disease Duration in Escalation Phase [ Time Frame: 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) ] [ Designated as safety issue: No ]
    If a participant had not achieved an objective response with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) - 1.1 as determined by the investigators, relative to the response evaluable population, but remained stable for at least 6 weeks after first dose, then the best overall response for such a participant was considered as stable disease.

  • Number of Participants With Stable Disease and Stable Disease Duration in Expansion Phase [ Time Frame: 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) ] [ Designated as safety issue: No ]
    If a participant had not achieved an objective response with confirmed complete response (CR) or partial response (PR) according to RECIST (1.1) as determined by the investigators, relative to the response evaluable population, but remained stable for at least 6 weeks after first dose, then the best overall response for such a participant was considered as stable disease.

  • Number of Participants With Objective Response Rate (ORR) in Escalation Phase [ Time Frame: 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) ] [ Designated as safety issue: No ]
    ORR was defined as the percent of participants with CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) determined by study physicians, relative to the response evaluable population. Participants were considered non-responders until proven otherwise. Thus, participants who: 1) Did not have CR or PR while on study, or 2) Did not have a post-baseline tumor evaluation, or 3) Received anti-tumor treatment other than the study medication prior to reaching a CR or PR, or 4) Died, in progress, or drop out for any reason prior to reaching a CR or PR, were counted as non-responders in the assessment of ORR. To be assigned a status of PR or CR, changes in tumor measurements in participants with responding tumors were confirmed by repeated tumor assessment that were performed 4 weeks after the criteria for response were first met.

  • Number of Participants With ORR in Expansion Phase [ Time Frame: 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) ] [ Designated as safety issue: No ]
    ORR was defined as the percent of participants with CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) determined by study physicians, relative to the response evaluable population. Participants were considered non-responders until proven otherwise. Thus, participants who: 1) Did not have CR or PR while on study, or 2) Did not have a post-baseline tumor evaluation, or 3) Received anti-tumor treatment other than the study medication prior to reaching a CR or PR, or 4) Died, in progress, or drop out for any reason prior to reaching a CR or PR, were counted as non-responders in the assessment of ORR. To be assigned a status of PR or CR, changes in tumor measurements in participants with responding tumors were confirmed by repeated tumor assessment that were performed 4 weeks after the criteria for response were first met.

  • Duration of Response for the Only Participant Shown Partial Response in Expansion Phase [ Time Frame: 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) ] [ Designated as safety issue: No ]
    This outcome measure presented the duration of response for one participant in expansion cohort 1 who showed partial response.

  • Progression Free Survival (PFS) in Escalation Phase [ Time Frame: From randomization to objective tumor progression or death (up to post treatment follow-up as 28-35 days after last dose of study treatment) ] [ Designated as safety issue: No ]
    PFS was defined as the time from the date of the first dose to the date of the first documentation of objective tumor progression according to RECIST 1.1 or death on study due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used.

  • Progression Free Survival (PFS) in Expansion Phase [ Time Frame: From randomization to objective tumor progression or death (up to post treatment follow-up as 28-35 days after last dose of study treatment) ] [ Designated as safety issue: No ]
    PFS was defined as the time from the date of the first dose to the date of the first documentation of objective tumor progression according to RECIST 1.1 or death on study due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used.

  • Expression Analysis of Tumor Biomarkers (HGF, EGFR, and c-Met ) at Baseline Using Immunohistochemistry (IHC) Method [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Tumor biomarkers such as HGF, EGFR, and c-Met were analyzed in tumor cells (neoplastic compartment) of tumor specimens from both expansion cohorts 1 and 2 by IHC. The H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+, where 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum calculated score of 0 to maximum calculated score of 300, where 0 correspond to no expression and maximum score of 300 indicates the strongest expression. However, the biomarker expression level (higher or lower) was not a predictor of outcome.

  • Expression Analysis of Tumor Biomarkers (EGFR, and c-Met) at Baseline Using Fluorescent in Situ Hybridization (FISH) Method [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Expression of tumor biomarkers EGFR and cMet at Baseline (using FISH method) are presented in this outcome measure.

  • Number of Participants With c-Met, HER2, EGFR Amplification and ALK Rearrangement at Baseline Using FISH Method [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Participants showed amplification of c-Met, HER2, and EGFR in the tumor cells and gene rearrangement of ALK are presented in this outcome measure.

  • Plasma Concentration of sMet by Study Visits [ Time Frame: At screening and Cycle 1 Day 1 (C1D1) (6 hours post dose), and C1D15, C2D1, C2D15 (all predose). ] [ Designated as safety issue: No ]
    This outcome measure presented the plasma concentration of sMet at different study visits. s-Met was analyzed using an enzyme-linked immunosorbent assay (ELISA).

  • Number of Participants With EGFR Mutation at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Sample analyses were performed in accordance to Good Laboratory Practice (GLP) guidance and included mutation detection for EGFR gene.

  • Number of Participants With KRAS Mutation (GLY12CYS) at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Sample analyses were performed in accordance to GLP guidance and included mutation detection for KRAS gene.

  • Number of Participants With PIK3CA Mutation at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Sample analyses were performed in accordance to GLP guidance and included mutation detection for PIK3CA gene.

  • Number of Participants With ROS1 Gene Translocation at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Sample analyses were performed in accordance to GLP guidance and included translocation detection (RNA based) for ROS1 gene.

  • 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) [ Time Frame: Cycle 1 (C1)/Day 1 (D1), C1D15 ] [ Designated as safety issue: No ]
    At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included AUClast for crizotinib and PF-06260182. AUClast was calculated using Linear/Log trapezoidal method.

  • Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Curve 10 (AUC10) [ Time Frame: C1D1, C1D15 ] [ Designated as safety issue: No ]
    At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). AUC10 was calculated using Linear/Log trapezoidal method. The below analysis table included geometric Mean and Geometric Coefficient of Variation of AUC10 for crizotinib and PF-06260182. Arithmetic mean was presented if the n=2.

  • Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Maximum Plasma Concentration (Cmax) [ Time Frame: C1D1, C1D15 ] [ Designated as safety issue: No ]
    At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Cmax for crizotinib and PF-06260182. Cmax was observed directly from data.

  • Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Time of Last Quantifiable Concentration (Tlast) [ Time Frame: C1D1, C1D15 ] [ Designated as safety issue: No ]
    At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Tlast for crizotinib and PF-06260182. Tlast was observed directly from data.

  • Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase -Time to Maximum Plasma Concentration (Tmax) [ Time Frame: C1D1, C1D15 ] [ Designated as safety issue: No ]
    At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Tmax for crizotinib and PF-06260182. Tmax was observed directly from data as time of first occurrence.

  • Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUClast [ Time Frame: C1D1, C1D15 ] [ Designated as safety issue: No ]
    At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included AUClast for dacomitinib and PF-05199265. AUClast was calculated using Linear/Log trapezoidal method.

  • Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUC24 [ Time Frame: C1D1, C1D15 ] [ Designated as safety issue: No ]
    At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included AUC24 for dacomitinib and PF-05199265. AUC24 was calculated using Linear/Log trapezoidal method.

  • Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Cmax [ Time Frame: C1D1, C1D15 ] [ Designated as safety issue: No ]
    At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Cmax for dacomitinib and PF-05199265. Cmax was observed directly from data.

  • Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tlast [ Time Frame: C1D1, C1D15 ] [ Designated as safety issue: No ]
    At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Tlast for dacomitinib and PF-05199265. Tlast was observed directly from data.

  • Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tmax [ Time Frame: C1D1, C1D15 ] [ Designated as safety issue: No ]
    At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Tmax for dacomitinib and PF-05199265. Tmax was observed directly from data as time of first occurrence.

  • Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - AUClast [ Time Frame: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib) ] [ Designated as safety issue: No ]
    Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for AUClast. AUClast was calculated using Linear/Log trapezoidal method.

  • Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - AUC10 [ Time Frame: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib) ] [ Designated as safety issue: No ]
    Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for AUC10. AUC10 was calculated using Linear/Log trapezoidal method.

  • Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Cmin [ Time Frame: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib) ] [ Designated as safety issue: No ]
    Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for Cmin. Cmin was observed directly from data.

  • Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Cmax [ Time Frame: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib) ] [ Designated as safety issue: No ]
    Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for Cmax. Cmax was observed directly from data.

  • Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Tlast [ Time Frame: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib) ] [ Designated as safety issue: No ]
    Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for Tlast. Tlast was observed directly from data.

  • Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Tmax [ Time Frame: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib) ] [ Designated as safety issue: No ]
    Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for Tmax. Tmax was observed directly from data as time of first occurrence.

  • Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - AUClast [ Time Frame: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib) ] [ Designated as safety issue: No ]
    PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (AUClast) following dacomitinib alone and in combination with crizotinib are summarized in the below table. AUClast was calculated using Linear/Log trapezoidal method.

  • Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - AUC24 [ Time Frame: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib) ] [ Designated as safety issue: No ]
    PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (AUC24) following dacomitinib alone and in combination with crizotinib are summarized in the below table. AUC24 was calculated using Linear/Log trapezoidal method.

  • Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Cmin [ Time Frame: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib) ] [ Designated as safety issue: No ]
    PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (Cmin) following dacomitinib alone and in combination with crizotinib are summarized in the below table. Cmin was observed directly from data.

  • Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Cmax [ Time Frame: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib) ] [ Designated as safety issue: No ]
    PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (Cmax) following dacomitinib alone and in combination with crizotinib are summarized in the below table. Cmax was observed directly from data.

  • Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Tlast [ Time Frame: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib) ] [ Designated as safety issue: No ]
    PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (Tlast) following dacomitinib alone and in combination with crizotinib are summarized in the below table. Tlast was observed directly from data.

  • Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Tmax [ Time Frame: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib) ] [ Designated as safety issue: No ]
    PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (Tmax) following dacomitinib alone and in combination with crizotinib are summarized in the below table. Tmax was observed directly from data as time of first occurrence.


Enrollment: 70
Study Start Date: August 2010
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
PF-02341066 AND PF-00299804: Patients will be treated with combined cMET inhibitor (PF-02341066) and panHER inhibitor (PF-00299804).
Drug: 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.
Other Name: cMET inhibitor
Drug: 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.
Other Name: panHER inhibitor
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).
Drug: 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).
Other Name: cMET inhibitor
Drug: 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).
Other Name: panHER inhibitor

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01121575

Locations
United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80045
DRUG SHIPMENT: University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
Rocky Mountain Lions Eye Institute
Aurora, Colorado, United States, 80045
Clinical Trials Office University of Colorado Hospital (CTO)
Aurora, Colorado, United States, 80045
United States, Maryland
CCR, National Cancer Institute
Bethesda, Maryland, United States, 20892
United States, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
Drug Shipment Only
Boston, Massachusetts, United States, 02114
Drug Shipment Only
Boston, Massachusetts, United States, 02215
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Australia, Victoria
Peter MacCallum Cancer Centre, Division of Haematology and Medical Oncology
East Melbourne, Victoria, Australia, 3002
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: NCT01121575     History of Changes
Other Study ID Numbers: A8081006
Study First Received: May 10, 2010
Results First Received: February 11, 2015
Last Updated: March 27, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Phase 1 acquired resistance to erlotinib or gefitinib cMET inhibitor EGFR inhibitor panHER inhibitor combination trial Crizotinib

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Crizotinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on May 26, 2015