An Investigational Drug, PF-02341066 Is Being Studied Versus Standard Of Care In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00932893
First received: June 30, 2009
Last updated: March 12, 2014
Last verified: March 2014
Results First Received: March 13, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Carcinoma, Non-Small-Cell Lung
Interventions: Drug: PF-02341066
Drug: Pemetrexed
Drug: Docetaxel

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Crizotinib Crizotinib (PF-02341066) 250 milligram (mg) (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Chemotherapy Pemetrexed 500 mg per square meter (mg/m^2) intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.

Participant Flow:   Overall Study
    Crizotinib     Chemotherapy  
STARTED     173     174  
Treated     172     171  
COMPLETED     0     0  
NOT COMPLETED     173     174  
Death                 46                 16  
Lost to Follow-up                 1                 0  
Withdrawal by Subject                 3                 2  
Unspecified                 5                 107  
Ongoing at Data Cut-off                 118                 49  



  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.
Full analysis set (FAS) included all participants who were randomized to study treatment.

Reporting Groups
  Description
Crizotinib Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Chemotherapy Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Total Total of all reporting groups

Baseline Measures
    Crizotinib     Chemotherapy     Total  
Number of Participants  
[units: participants]
  173     174     347  
Age  
[units: years]
Mean ± Standard Deviation
  50.31  ± 13.1     49.81  ± 13.0     50.06  ± 13.0  
Gender  
[units: participants]
     
Female     98     96     194  
Male     75     78     153  



  Outcome Measures
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1.  Primary:   Progression-Free Survival (PFS)   [ Time Frame: Randomization until progressive disease (PD) or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks) ]

2.  Secondary:   Overall Survival (OS)   [ Time Frame: Randomization until death (up to 112 weeks) ]

3.  Secondary:   Overall Survival Probability at Month 6 and Month 12   [ Time Frame: Month 6, 12 ]

4.  Secondary:   Percentage of Participants With Objective Response (OR)   [ Time Frame: Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks) ]

5.  Secondary:   Percentage of Participants With Disease Control at Week 6   [ Time Frame: Week 6 ]

6.  Secondary:   Percentage of Participants With Disease Control at Week 12   [ Time Frame: Week 12 ]

7.  Secondary:   Duration of Response (DR)   [ Time Frame: Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks) ]

8.  Secondary:   Time to Tumor Response (TTR)   [ Time Frame: Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks) ]

9.  Secondary:   Pre-Dose Plasma Concentration (Ctrough) of Crizotinib   [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2, 3, 5 ]

10.  Secondary:   Pre-Dose Plasma Concentration at Steady State (Ctrough, ss) of Crizotinib   [ Time Frame: Pre-dose on Day 15 of Cycle 1 ]

11.  Secondary:   Number of Participants With Categorical Maximum QTcF for Crizotinib   [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2 to 6 hours post-dose on Day 1 of Cycle 1, 2 ]

12.  Secondary:   Time to Deterioration (TTD) in Participant Reported Pain, Dyspnea, and Cough   [ Time Frame: Baseline up to end of treatment (up to 112 weeks) ]

13.  Secondary:   European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)   [ Time Frame: Baseline, Day (D) 1 of each cycle (C) until disease progression, end of treatment (EOT, up to 112 weeks) ]

14.  Secondary:   European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Supplement Module for Lung Cancer (EORTC QLQ-LC13)   [ Time Frame: Baseline, Day 1 of each cycle until disease progression, end of treatment (up to 112 weeks) ]

15.  Secondary:   European Quality of Life - 5 Dimensional (EQ-5D) Visual Analog Scale (VAS)   [ Time Frame: Baseline, Day 1 of each cycle until disease progression, end of treatment (up to 112 weeks) ]
  Hide Outcome Measure 15

Measure Type Secondary
Measure Title European Quality of Life - 5 Dimensional (EQ-5D) Visual Analog Scale (VAS)
Measure Description EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.
Time Frame Baseline, Day 1 of each cycle until disease progression, end of treatment (up to 112 weeks)  
Safety Issue No  

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.
FAS included all participants who were randomized to study treatment. Here “N” (number of participants analyzed) signifies participants who were evaluable for this measure and “n” signifies participants who were evaluable for specified time points for each arm group, respectively.

Reporting Groups
  Description
Crizotinib Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Chemotherapy Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.

Measured Values
    Crizotinib     Chemotherapy  
Number of Participants Analyzed  
[units: participants]
  164     161  
European Quality of Life - 5 Dimensional (EQ-5D) Visual Analog Scale (VAS)  
[units: units on a scale]
Mean ± Standard Deviation
   
Baseline (n=164, 161)     64.09  ± 21.04     66.76  ± 20.74  
C2D1 (n=153, 131)     69.19  ± 19.42     66.33  ± 20.30  
C3D1 (n=153, 105)     73.13  ± 18.97     65.84  ± 20.80  
C4D1 (n=135, 90)     73.78  ± 18.25     69.13  ± 18.14  
C5D1 (n=122, 74)     75.27  ± 17.99     68.12  ± 23.19  
C6D1 (n=120, 70)     75.79  ± 18.67     69.71  ± 22.46  
C7D1 (n=115, 52)     77.02  ± 17.34     70.63  ± 24.31  
C8D1 (n=110, 43)     74.72  ± 18.09     72.30  ± 23.54  
C9D1 (n=101, 37)     74.45  ± 18.32     72.27  ± 25.85  
C10D1 (n=94, 33)     75.49  ± 18.18     74.27  ± 24.88  
C11D1 (n=84, 25)     76.32  ± 17.00     77.24  ± 20.31  
C12D1 (n=77, 23)     76.95  ± 17.63     74.83  ± 22.60  
C13D1 (n=73, 21)     76.38  ± 17.50     73.00  ± 23.54  
C14D1 (n=66, 19)     78.77  ± 15.54     74.11  ± 22.56  
C15D1 (n=62, 16)     77.71  ± 16.78     77.44  ± 19.52  
C16D1 (n=53, 12)     75.32  ± 16.21     79.00  ± 13.28  
C17D1 (n=47, 11)     75.09  ± 17.68     81.73  ± 15.98  
C18D1 (n=45, 11)     75.87  ± 16.63     78.91  ± 16.25  
C19D1 (n=40, 9)     76.85  ± 16.39     78.00  ± 14.04  
C20D1 (n=35, 8)     72.66  ± 19.81     76.75  ± 17.65  
C21D1 (n=30, 8)     74.13  ± 16.19     73.63  ± 19.41  
C22D1 (n=24, 7)     77.54  ± 17.54     72.21  ± 19.79  
C23D1 (n=23, 4)     75.48  ± 17.75     54.00  ± 16.35  
C24D1 (n=20, 3)     71.40  ± 23.15     62.00  ± 20.30  
C25D1 (n=18, 3)     75.61  ± 15.97     63.67  ± 22.59  
C26D1 (n=14, 3)     72.14  ± 20.71     63.00  ± 17.52  
C27D1 (n=14, 2)     66.57  ± 16.96     50.00  ± 14.14  
C28D1 (n=11, 2)     72.36  ± 12.72     55.00  ± 21.21  
C29D1 (n=8, 2)     71.38  ± 12.28     45.00  ± 14.14  
C30D1 (n=8, 1)     69.50  ± 17.00     40.00  ± NA [1]
C31D1 (n=7, 0)     68.57  ± 16.76     NA  ± NA [2]
C32D1 (n=6, 0)     65.83  ± 19.41     NA  ± NA [2]
C33D1 (n=6, 0)     67.50  ± 20.34     NA  ± NA [2]
C34D1 (n=5, 0)     68.00  ± 20.80     NA  ± NA [2]
C35D1 (n=4, 0)     72.25  ± 14.84     NA  ± NA [2]
C36D1 (n=1, 0)     90.00  ± NA [1]   NA  ± NA [2]
C37D1 (n=1, 0)     85.00  ± NA [1]   NA  ± NA [2]
EOT (n=49, 90)     68.33  ± 21.25     58.34  ± 23.71  
[1] Standard deviation was not estimable since only one participant was evaluable
[2] Data was not analyzed as no participants were evaluable

No statistical analysis provided for European Quality of Life - 5 Dimensional (EQ-5D) Visual Analog Scale (VAS)



16.  Secondary:   Percentage of Participants With Echinoderm Microtubule Associated Protein-Like 4-Anaplastic Lymphoma Kinase (EML4-ALK) Fusion Variants   [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2 to 6 hours post-dose on Day 1 of Cycle 2, end of treatment (up to 112 weeks) ]
Results not yet posted.   Anticipated Posting Date:   12/2015   Safety Issue:   No

17.  Secondary:   Plasma Concentration of Soluble c-Met Ectodomain and Hepatocyte Growth Factor Scatter Proteins   [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2 to 6 hours post-dose on Day 1 of Cycle 2, end of treatment (up to 112 weeks) ]
Results not yet posted.   Anticipated Posting Date:   12/2015   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


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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.


Limitations and Caveats
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
These results are from a preliminary clinical study report including final results for PFS and interim results for OS.  


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


No publications provided by Pfizer

Publications automatically indexed to this study:

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00932893     History of Changes
Other Study ID Numbers: A8081007
Study First Received: June 30, 2009
Results First Received: March 13, 2013
Last Updated: March 12, 2014
Health Authority: United States: Food and Drug Administration