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: June 25, 2014
Last verified: June 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) ]

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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Time Frame No text entered.
Additional Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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.

Other Adverse Events
    Crizotinib     Chemotherapy  
Total, other (not including serious) adverse events      
# participants affected / at risk     169/172     154/171  
Blood and lymphatic system disorders      
Anaemia * 1    
# participants affected / at risk     25/172 (14.53%)     26/171 (15.20%)  
Leukopenia * 1    
# participants affected / at risk     15/172 (8.72%)     9/171 (5.26%)  
Neutropenia * 1    
# participants affected / at risk     35/172 (20.35%)     17/171 (9.94%)  
Eye disorders      
Photopsia * 1    
# participants affected / at risk     17/172 (9.88%)     1/171 (0.58%)  
Vision blurred * 1    
# participants affected / at risk     14/172 (8.14%)     5/171 (2.92%)  
Visual impairment * 1    
# participants affected / at risk     81/172 (47.09%)     9/171 (5.26%)  
Gastrointestinal disorders      
Abdominal pain * 1    
# participants affected / at risk     15/172 (8.72%)     8/171 (4.68%)  
Abdominal pain upper * 1    
# participants affected / at risk     9/172 (5.23%)     12/171 (7.02%)  
Constipation * 1    
# participants affected / at risk     73/172 (42.44%)     39/171 (22.81%)  
Diarrhoea * 1    
# participants affected / at risk     103/172 (59.88%)     33/171 (19.30%)  
Dyspepsia * 1    
# participants affected / at risk     14/172 (8.14%)     6/171 (3.51%)  
Nausea * 1    
# participants affected / at risk     94/172 (54.65%)     62/171 (36.26%)  
Stomatitis * 1    
# participants affected / at risk     7/172 (4.07%)     12/171 (7.02%)  
Vomiting * 1    
# participants affected / at risk     79/172 (45.93%)     30/171 (17.54%)  
General disorders      
Asthenia * 1    
# participants affected / at risk     25/172 (14.53%)     32/171 (18.71%)  
Chest pain * 1    
# participants affected / at risk     9/172 (5.23%)     12/171 (7.02%)  
Fatigue * 1    
# participants affected / at risk     46/172 (26.74%)     56/171 (32.75%)  
Oedema * 1    
# participants affected / at risk     11/172 (6.40%)     5/171 (2.92%)  
Oedema peripheral * 1    
# participants affected / at risk     44/172 (25.58%)     14/171 (8.19%)  
Pyrexia * 1    
# participants affected / at risk     30/172 (17.44%)     32/171 (18.71%)  
Infections and infestations      
Nasopharyngitis * 1    
# participants affected / at risk     24/172 (13.95%)     6/171 (3.51%)  
Upper respiratory tract infection * 1    
# participants affected / at risk     16/172 (9.30%)     15/171 (8.77%)  
Investigations      
Alanine aminotransferase increased * 1    
# participants affected / at risk     62/172 (36.05%)     20/171 (11.70%)  
Aspartate aminotransferase increased * 1    
# participants affected / at risk     45/172 (26.16%)     16/171 (9.36%)  
Blood alkaline phosphatase increased * 1    
# participants affected / at risk     13/172 (7.56%)     6/171 (3.51%)  
Blood creatinine increased * 1    
# participants affected / at risk     12/172 (6.98%)     3/171 (1.75%)  
Neutrophil count decreased * 1    
# participants affected / at risk     12/172 (6.98%)     9/171 (5.26%)  
Weight decreased * 1    
# participants affected / at risk     17/172 (9.88%)     6/171 (3.51%)  
White blood cell count decreased * 1    
# participants affected / at risk     12/172 (6.98%)     13/171 (7.60%)  
Metabolism and nutrition disorders      
Decreased appetite * 1    
# participants affected / at risk     47/172 (27.33%)     44/171 (25.73%)  
Hyperglycaemia * 1    
# participants affected / at risk     5/172 (2.91%)     9/171 (5.26%)  
Hypoalbuminaemia * 1    
# participants affected / at risk     11/172 (6.40%)     1/171 (0.58%)  
Hypokalaemia * 1    
# participants affected / at risk     9/172 (5.23%)     4/171 (2.34%)  
Musculoskeletal and connective tissue disorders      
Arthralgia * 1    
# participants affected / at risk     11/172 (6.40%)     20/171 (11.70%)  
Back pain * 1    
# participants affected / at risk     18/172 (10.47%)     12/171 (7.02%)  
Musculoskeletal pain * 1    
# participants affected / at risk     12/172 (6.98%)     5/171 (2.92%)  
Myalgia * 1    
# participants affected / at risk     3/172 (1.74%)     18/171 (10.53%)  
Pain in extremity * 1    
# participants affected / at risk     9/172 (5.23%)     10/171 (5.85%)  
Nervous system disorders      
Dizziness * 1    
# participants affected / at risk     28/172 (16.28%)     12/171 (7.02%)  
Dysgeusia * 1    
# participants affected / at risk     44/172 (25.58%)     16/171 (9.36%)  
Headache * 1    
# participants affected / at risk     32/172 (18.60%)     25/171 (14.62%)  
Neuropathy peripheral * 1    
# participants affected / at risk     4/172 (2.33%)     9/171 (5.26%)  
Paraesthesia * 1    
# participants affected / at risk     10/172 (5.81%)     7/171 (4.09%)  
Psychiatric disorders      
Insomnia * 1    
# participants affected / at risk     18/172 (10.47%)     14/171 (8.19%)  
Respiratory, thoracic and mediastinal disorders      
Cough * 1    
# participants affected / at risk     28/172 (16.28%)     33/171 (19.30%)  
Dyspnoea * 1    
# participants affected / at risk     18/172 (10.47%)     28/171 (16.37%)  
Epistaxis * 1    
# participants affected / at risk     2/172 (1.16%)     10/171 (5.85%)  
Haemoptysis * 1    
# participants affected / at risk     6/172 (3.49%)     11/171 (6.43%)  
Oropharyngeal pain * 1    
# participants affected / at risk     13/172 (7.56%)     7/171 (4.09%)  
Rhinorrhoea * 1    
# participants affected / at risk     4/172 (2.33%)     9/171 (5.26%)  
Skin and subcutaneous tissue disorders      
Alopecia * 1    
# participants affected / at risk     14/172 (8.14%)     35/171 (20.47%)  
Dry skin * 1    
# participants affected / at risk     9/172 (5.23%)     2/171 (1.17%)  
Pruritus * 1    
# participants affected / at risk     9/172 (5.23%)     7/171 (4.09%)  
Rash * 1    
# participants affected / at risk     15/172 (8.72%)     29/171 (16.96%)  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 15.0



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


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