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: September 9, 2014
Last verified: September 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 reported.   Anticipated Reporting 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 reported.   Anticipated Reporting Date:   12/2015   Safety Issue:   No


  Serious 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.

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.

Serious Adverse Events
    Crizotinib     Chemotherapy  
Total, serious adverse events      
# participants affected / at risk     64/172 (37.21%)     40/171 (23.39%)  
Blood and lymphatic system disorders      
Anaemia * 1    
# participants affected / at risk     1/172 (0.58%)     2/171 (1.17%)  
Febrile neutropenia * 1    
# participants affected / at risk     1/172 (0.58%)     12/171 (7.02%)  
Neutropenia * 1    
# participants affected / at risk     2/172 (1.16%)     2/171 (1.17%)  
Thrombocytopenia * 1    
# participants affected / at risk     0/172 (0.00%)     1/171 (0.58%)  
Cardiac disorders      
Arrhythmia * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Cardiac arrest * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Cardiac tamponade * 1    
# participants affected / at risk     0/172 (0.00%)     1/171 (0.58%)  
Pericardial effusion * 1    
# participants affected / at risk     1/172 (0.58%)     2/171 (1.17%)  
Supraventricular tachycardia * 1    
# participants affected / at risk     0/172 (0.00%)     1/171 (0.58%)  
Gastrointestinal disorders      
Abdominal pain upper * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Diarrhoea * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Ileus paralytic * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Intestinal perforation * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Nausea * 1    
# participants affected / at risk     1/172 (0.58%)     2/171 (1.17%)  
Oesophageal stenosis * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Stomatitis * 1    
# participants affected / at risk     0/172 (0.00%)     1/171 (0.58%)  
Vomiting * 1    
# participants affected / at risk     2/172 (1.16%)     0/171 (0.00%)  
General disorders      
Pleural Drain Colonization * 1    
# participants affected / at risk     0/172 (0.00%)     1/171 (0.58%)  
Recurrent Viscous Pleural Effusion * 1    
# participants affected / at risk     0/172 (0.00%)     1/171 (0.58%)  
Chest pain * 1    
# participants affected / at risk     0/172 (0.00%)     2/171 (1.17%)  
Death * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Disease progression * 1    
# participants affected / at risk     13/172 (7.56%)     3/171 (1.75%)  
Fatigue * 1    
# participants affected / at risk     1/172 (0.58%)     1/171 (0.58%)  
Mucosal inflammation * 1    
# participants affected / at risk     0/172 (0.00%)     2/171 (1.17%)  
Pyrexia * 1    
# participants affected / at risk     1/172 (0.58%)     1/171 (0.58%)  
Sudden death * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Hepatobiliary disorders      
Hepatic failure * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Hepatitis * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Infections and infestations      
Empyema * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Extradural abscess * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Lower respiratory tract infection * 1    
# participants affected / at risk     2/172 (1.16%)     2/171 (1.17%)  
Lung abscess * 1    
# participants affected / at risk     2/172 (1.16%)     0/171 (0.00%)  
Lung infection * 1    
# participants affected / at risk     2/172 (1.16%)     1/171 (0.58%)  
Pneumonia * 1    
# participants affected / at risk     7/172 (4.07%)     3/171 (1.75%)  
Pneumonia bacterial * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Sepsis * 1    
# participants affected / at risk     1/172 (0.58%)     1/171 (0.58%)  
Urinary tract infection * 1    
# participants affected / at risk     0/172 (0.00%)     1/171 (0.58%)  
Injury, poisoning and procedural complications      
Femur fracture * 1    
# participants affected / at risk     1/172 (0.58%)     1/171 (0.58%)  
Spinal fracture * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Investigations      
Alanine aminotransferase increased * 1    
# participants affected / at risk     2/172 (1.16%)     0/171 (0.00%)  
Aspartate aminotransferase increased * 1    
# participants affected / at risk     2/172 (1.16%)     0/171 (0.00%)  
Blood glucose increased * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Electrocardiogram QT prolonged * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Haemoglobin decreased * 1    
# participants affected / at risk     0/172 (0.00%)     1/171 (0.58%)  
Neutrophil count decreased * 1    
# participants affected / at risk     0/172 (0.00%)     1/171 (0.58%)  
White blood cell count decreased * 1    
# participants affected / at risk     0/172 (0.00%)     2/171 (1.17%)  
Metabolism and nutrition disorders      
Decreased appetite * 1    
# participants affected / at risk     1/172 (0.58%)     1/171 (0.58%)  
Hyperglycaemia * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Hyperkalaemia * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Hypoglycaemia * 1    
# participants affected / at risk     2/172 (1.16%)     1/171 (0.58%)  
Hypokalaemia * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Musculoskeletal and connective tissue disorders      
Back pain * 1    
# participants affected / at risk     2/172 (1.16%)     2/171 (1.17%)  
Muscular weakness * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Musculoskeletal pain * 1    
# participants affected / at risk     0/172 (0.00%)     1/171 (0.58%)  
Spinal column stenosis * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Non-small cell lung cancer * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Tumour haemorrhage * 1    
# participants affected / at risk     0/172 (0.00%)     1/171 (0.58%)  
Nervous system disorders      
Brain oedema * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Cognitive disorder * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Convulsion * 1    
# participants affected / at risk     2/172 (1.16%)     1/171 (0.58%)  
Headache * 1    
# participants affected / at risk     0/172 (0.00%)     2/171 (1.17%)  
Intracranial pressure increased * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Lethargy * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Paraesthesia * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Syncope * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Psychiatric disorders      
Confusional state * 1    
# participants affected / at risk     0/172 (0.00%)     1/171 (0.58%)  
Mental status changes * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Renal and urinary disorders      
Renal cyst * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Respiratory, thoracic and mediastinal disorders      
Acute respiratory distress syndrome * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Acute respiratory failure * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Cough * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Dyspnoea * 1    
# participants affected / at risk     4/172 (2.33%)     2/171 (1.17%)  
Interstitial lung disease * 1    
# participants affected / at risk     3/172 (1.74%)     0/171 (0.00%)  
Organising pneumonia * 1    
# participants affected / at risk     0/172 (0.00%)     1/171 (0.58%)  
Pleural effusion * 1    
# participants affected / at risk     1/172 (0.58%)     2/171 (1.17%)  
Pneumonitis * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Pulmonary artery thrombosis * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Pulmonary embolism * 1    
# participants affected / at risk     5/172 (2.91%)     3/171 (1.75%)  
Pulmonary oedema * 1    
# participants affected / at risk     0/172 (0.00%)     1/171 (0.58%)  
Pulmonary thrombosis * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Respiratory failure * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Skin and subcutaneous tissue disorders      
Drug eruption * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Surgical and medical procedures      
Malignant tumour excision * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
Vascular disorders      
Deep vein thrombosis * 1    
# participants affected / at risk     1/172 (0.58%)     2/171 (1.17%)  
Pelvic venous thrombosis * 1    
# participants affected / at risk     1/172 (0.58%)     0/171 (0.00%)  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 15.0




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


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