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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 has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00932893
First received: June 30, 2009
Last updated: October 31, 2016
Last verified: October 2016
Results First Received: March 13, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   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 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   40   4 
NOT COMPLETED   133   170 
Death                115                24 
Lost to Follow-up                8                0 
Withdrawal by Subject                5                2 
Unspecified                5                144 



  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 
Overall Participants Analyzed 
[Units: Participants]
 173   174   347 
Age 
[Units: Years]
Mean (Standard Deviation)
 50.3  (13.1)   49.8  (13.0)   50.0  (13.0) 
Gender 
[Units: Participants]
Count of Participants
     
Female      98  56.6%      95  54.6%      193  55.6% 
Male      75  43.4%      79  45.4%      154  44.4% 


  Outcome Measures
  Show All Outcome Measures

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 4.5 years) ]

3.  Secondary:   Overall Survival Probability at Months 6 and 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:   Plasma Concentration of Crizotinib   [ Time Frame: Pre-dose on Cycle 1 Day 1, Cycle 1 Day 15, and Day 1 of Cycles 2, 3, 5 ]

10.  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 ]

11.  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) ]

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) ]


  Serious Adverse Events
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Time Frame Active reporting period is from the time of informed consent until at least 28 days after the last dose of study treatment.
Additional Description All causality (serious and non-serious) adverse events have been reported. Non-serious adverse events above the 5% threshold are reported herein.

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   80/172 (46.51%)   42/171 (24.56%) 
Blood and lymphatic system disorders     
Anaemia * 1     
# participants affected / at risk   2/172 (1.16%)   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%) 
Lymphadenopathy * 1     
# participants affected / at risk   1/172 (0.58%)   0/171 (0.00%) 
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   1/172 (0.58%)   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%) 
Coronary artery disease * 1     
# participants affected / at risk   1/172 (0.58%)   0/171 (0.00%) 
Myocardial ischaemia * 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%) 
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   3/172 (1.74%)   0/171 (0.00%) 
Food poisoning * 1     
# participants affected / at risk   1/172 (0.58%)   0/171 (0.00%) 
Haematemesis * 1     
# participants affected / at risk   1/172 (0.58%)   0/171 (0.00%) 
Melaena * 1     
# participants affected / at risk   0/172 (0.00%)   1/171 (0.58%) 
General disorders     
Product contamination microbial * 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   2/172 (1.16%)   0/171 (0.00%) 
Disease progression * 1     
# participants affected / at risk   18/172 (10.47%)   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%) 
General physical health deterioration * 1     
# participants affected / at risk   1/172 (0.58%)   0/171 (0.00%) 
Malaise * 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   8/172 (4.65%)   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%) 
Cellulitis * 1     
# participants affected / at risk   2/172 (1.16%)   0/171 (0.00%) 
Gastroenteritis * 1     
# participants affected / at risk   1/172 (0.58%)   0/171 (0.00%) 
Pneumonia influenzal * 1     
# participants affected / at risk   1/172 (0.58%)   0/171 (0.00%) 
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   3/172 (1.74%)   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 * 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   2/172 (1.16%)   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)     
Tumour haemorrhage * 1     
# participants affected / at risk   0/172 (0.00%)   1/171 (0.58%) 
Colon cancer * 1     
# participants affected / at risk   0/172 (0.00%)   1/171 (0.58%) 
Colon cancer recurrent * 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%) 
Headache * 1     
# participants affected / at risk   1/172 (0.58%)   2/171 (1.17%) 
Intracranial pressure increased * 1     
# participants affected / at risk   2/172 (1.16%)   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%) 
Presyncope * 1     
# participants affected / at risk   1/172 (0.58%)   0/171 (0.00%) 
Cerebral cyst * 1     
# participants affected / at risk   1/172 (0.58%)   0/171 (0.00%) 
Dizziness * 1     
# participants affected / at risk   1/172 (0.58%)   0/171 (0.00%) 
Seizure * 1     
# participants affected / at risk   2/172 (1.16%)   1/171 (0.58%) 
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%) 
Delirium * 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%) 
Ureteric stenosis * 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   6/172 (3.49%)   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   2/172 (1.16%)   3/171 (1.75%) 
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   7/172 (4.07%)   3/171 (1.75%) 
Pulmonary oedema * 1     
# participants affected / at risk   0/172 (0.00%)   1/171 (0.58%) 
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     
Cancer surgery * 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 18.1




  Other Adverse Events


  Limitations and Caveats
  Hide 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
No analyses of ALK fusion variants or protein expression were done due to limited slide stability of unstained tissue sections required for immunohistochemistry and no nucleic acid based assay was available to identify specific ALK gene fusion.


  More Information