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: October 6, 2015
Last verified: October 2015
Results First Received: February 11, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Non Small Cell Lung Cancer
Interventions: Drug: PF-02341066
Drug: PF-00299804

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This was a Phase 1, multicenter, open-label, non-randomized study of combined oral crizotinib and oral dacomitinib in participants with advanced non-small cell lung cancer (NSCLC). The study consisted of a dose Escalation Phase and an Expansion Phase. The Expansion Phase consisted of Expansion Cohort 1 and 2 which ran concurrently.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 70 participants were enrolled and received study treatment in the United States (3 centers) and Australia (1 center). 33 participants in Escalation Phase and 37 participants in Expansion Phase (25 participants in Cohort 1 and 12 participants in Cohort 2) received treatment. The last participant completed the study on 11 Feb 2014.

Reporting Groups
  Description
Crizotinib 200 mg BID/ Dacomitinib 30 mg QD Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg twice a day (BID) and oral dacomitinib 30 mg once daily (QD). The first cycle was for 28 days thereafter, each cycle was 21 days.
Crizotinib 200 mg BID/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Expansion Cohort 1 Participants enrolled in expansion cohort 1 received combined oral crizotinib and oral dacomitinib on a continuous daily schedule of crizotinib 200 mg BID + dacomitinib 30 mg QD. Each cycle was 21 days. If there was unacceptable toxicity or tolerability the dose could be adjusted to a lower combined dose. Expansion Cohort 1 was designed to examine the safety of crizotinib and dacomitinib administered concomitantly in NSCLC participants with acquired resistance to erlotinib or gefitinib.
Expansion Cohort 2 Participants were treated first with single agent dacomitinib at a dose determined by agreement between the investigator and the sponsor, and then, at progression, with combined maximum tolerated dose of crizotinib and dacomitinib (given orally on a continuous schedule in 21-day cycles of crizotinib 200 mg BID + dacomitinib 30 mg QD) as soon as feasible, and no later than 28 days after documentation of progressive disease. Expansion Cohort 2 used the same participant population as Expansion Cohort 1 and was designed to assess the clinical value of adding crizotinib to dacomitinib treatment after disease progression on dacomitinib alone.

Participant Flow:   Overall Study
    Crizotinib 200 mg BID/ Dacomitinib 30 mg QD     Crizotinib 200 mg BID/ Dacomitinib 45 mg QD     Crizotinib 250 mg BID/ Dacomitinib 30 mg QD     Crizotinib 250 mg QD/ Dacomitinib 45 mg QD     Expansion Cohort 1     Expansion Cohort 2  
STARTED     14     6     7     6     25     12  
Treated     14     6     7     6     25     12  
COMPLETED     0     0     0     0     0     0  
NOT COMPLETED     14     6     7     6     25     12  
Participant Refused Further Follow-Up                 0                 0                 0                 0                 5                 1  
Unspecified Reasons                 8                 6                 7                 5                 13                 10  
Death                 6                 0                 0                 1                 7                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Crizotinib 200 mg BID/ Dacomitinib 30 mg QD Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Crizotinib 200 mg BID/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Expansion Cohort 1 Participants enrolled in expansion cohort 1 received combined oral crizotinib and oral dacomitinib on a continuous daily schedule of crizotinib 200 mg BID + dacomitinib 30 mg QD. Each cycle was 21 days. If there was unacceptable toxicity or tolerability the dose could be adjusted to a lower combined dose. Expansion Cohort 1 was designed to examine the safety of crizotinib and dacomitinib administered concomitantly in NSCLC participants with acquired resistance to erlotinib or gefitinib.
Expansion Cohort 2 Participants were treated first with single agent dacomitinib at a dose determined by agreement between the investigator and the sponsor, and then, at progression, with combined maximum tolerated dose of crizotinib and dacomitinib (given orally on a continuous schedule in 21-day cycles of crizotinib 200 mg BID + dacomitinib 30 mg QD) as soon as feasible, and no later than 28 days after documentation of progressive disease. Expansion Cohort 2 used the same participant population as Expansion Cohort 1 and was designed to assess the clinical value of adding crizotinib to dacomitinib treatment after disease progression on dacomitinib alone.
Total Total of all reporting groups

Baseline Measures
    Crizotinib 200 mg BID/ Dacomitinib 30 mg QD     Crizotinib 200 mg BID/ Dacomitinib 45 mg QD     Crizotinib 250 mg BID/ Dacomitinib 30 mg QD     Crizotinib 250 mg QD/ Dacomitinib 45 mg QD     Expansion Cohort 1     Expansion Cohort 2     Total  
Number of Participants  
[units: participants]
  14     6     7     6     25     12     70  
Age  
[units: Years]
Mean (Standard Deviation)
  53.6  (9.87)     61.7  (7.53)     54.7  (11.34)     62.2  (13.61)     61.8  (10.83)     59.6  (11.74)     59.1  (11.05)  
Gender  
[units: Participants]
             
Female     5     5     6     2     16     9     43  
Male     9     1     1     4     9     3     27  



  Outcome Measures
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1.  Primary:   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) ]

2.  Primary:   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) ]

3.  Primary:   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) ]

4.  Primary:   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) ]

5.  Primary:   Number of Participants With Dose Limiting Toxicities (DLTs) in Escalation Phase   [ Time Frame: Cycle 1 (4 weeks) ]

6.  Secondary:   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) ]

7.  Secondary:   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) ]

8.  Secondary:   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) ]

9.  Secondary:   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) ]

10.  Secondary:   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) ]

11.  Secondary:   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) ]

12.  Secondary:   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) ]

13.  Secondary:   Expression Analysis of Tumor Biomarkers (HGF, EGFR, and c-Met ) at Baseline Using Immunohistochemistry (IHC) Method   [ Time Frame: Baseline ]

14.  Secondary:   Expression Analysis of Tumor Biomarkers (EGFR, and c-Met) at Baseline Using Fluorescent in Situ Hybridization (FISH) Method   [ Time Frame: Baseline ]

15.  Secondary:   Number of Participants With c-Met, HER2, EGFR Amplification and ALK Rearrangement at Baseline Using FISH Method   [ Time Frame: Baseline ]

16.  Secondary:   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). ]

17.  Secondary:   Number of Participants With EGFR Mutation at Baseline   [ Time Frame: Baseline ]

18.  Secondary:   Number of Participants With KRAS Mutation (GLY12CYS) at Baseline   [ Time Frame: Baseline ]

19.  Secondary:   Number of Participants With PIK3CA Mutation at Baseline   [ Time Frame: Baseline ]

20.  Secondary:   Number of Participants With ROS1 Gene Translocation at Baseline   [ Time Frame: Baseline ]

21.  Secondary:   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 ]

22.  Secondary:   Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Curve 10 (AUC10)   [ Time Frame: C1D1, C1D15 ]

23.  Secondary:   Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Maximum Plasma Concentration (Cmax)   [ Time Frame: C1D1, C1D15 ]

24.  Secondary:   Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Time of Last Quantifiable Concentration (Tlast)   [ Time Frame: C1D1, C1D15 ]

25.  Secondary:   Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase -Time to Maximum Plasma Concentration (Tmax)   [ Time Frame: C1D1, C1D15 ]

26.  Secondary:   Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUClast   [ Time Frame: C1D1, C1D15 ]

27.  Secondary:   Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUC24   [ Time Frame: C1D1, C1D15 ]

28.  Secondary:   Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Cmax   [ Time Frame: C1D1, C1D15 ]

29.  Secondary:   Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tlast   [ Time Frame: C1D1, C1D15 ]

30.  Secondary:   Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tmax   [ Time Frame: C1D1, C1D15 ]

31.  Secondary:   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) ]

32.  Secondary:   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) ]

33.  Secondary:   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) ]

34.  Secondary:   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) ]

35.  Secondary:   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) ]

36.  Secondary:   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) ]

37.  Secondary:   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) ]

38.  Secondary:   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) ]

39.  Secondary:   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) ]

40.  Secondary:   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) ]

41.  Secondary:   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) ]

42.  Secondary:   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) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com



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: October 6, 2015
Health Authority: United States: Food and Drug Administration