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Study of Pemetrexed in Mesothelioma and Lung Cancer Patients With Fluid Around the Lungs or Abdomen

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ClinicalTrials.gov Identifier: NCT00316225
Recruitment Status : Completed
First Posted : April 20, 2006
Results First Posted : July 9, 2010
Last Update Posted : July 9, 2010
Sponsor:
Information provided by:
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Non-small Cell Lung Cancer
Mesothelioma
Lung Neoplasms
Intervention Drug: pemetrexed
Enrollment 31
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Pemetrexed
Hide Arm/Group Description Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Period Title: Overall Study
Started 31
Completed 6
Not Completed 25
Reason Not Completed
Adverse Event             2
Physician Decision             3
Progressive Disease             15
Withdrawal by Subject             3
Death             2
Arm/Group Title Pemetrexed
Hide Arm/Group Description Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Overall Number of Baseline Participants 31
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 31 participants
62.7
(35.7 to 77.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants
Female
4
  12.9%
Male
27
  87.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 31 participants
Caucasian 30
Hispanic 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 31 participants
Spain 12
Denmark 6
Germany 13
Diagnosis   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 31 participants
Non-Small Cell Lung Cancer (NSCLC) 23
Mesothelioma 8
[1]
Measure Description: Diagnosis of Non-Small Cell Lung Cancer (NSCLC) and mesothelioma were determined by each individual investigator.
Disease Stage   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 31 participants
Stage III (locally advanced disease) 12
Stage IV (metastatic disease) 18
Unknown 1
[1]
Measure Description: Stage means how big the tumor is and how far it has spread. Stages range from 0 (not spread) to IV (spread throughout the body).
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 31 participants
0 - Fully Active 14
1 - Ambulatory, Restricted Strenuous Activity 17
[1]
Measure Description: Classifies patients according to their functional impairment. Scores range from 0 (Fully Active) to 5 (Death).
Fluid Severity   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 31 participants
Mild 15
Moderate 14
Severe 2
[1]
Measure Description:

Mild = (1) pleural effusion detectable on radiological imaging, but less than moderate; (2) ascites detectable only by radiological imaging. Moderate = (1) pleural effusion less than 1/3 of the way up the thorax on 1 side on imaging and obscuring the entire hemidiaphragm on that side; (2) ascites detectable on physical exam (that is, fluid wave is palpable). Severe = (1) pleural effusion more than 1/3 of the way up the thorax on imaging; (2) ascites visibly detectable.

For Moderate Fluid Severity, there were 13 patients with pleural effusion and 1 patient with ascites.
Primary Basis for Diagnosis  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 31 participants
Cytological 6
Histopathological 25
Type of Third-Space Fluid  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 31 participants
Pleural Effusion 30
Ascites 1
Body Surface Area  
Median (Full Range)
Unit of measure:  Meters squared (m^2)
Number Analyzed 31 participants
1.8
(1.4 to 2.3)
Height  
Median (Full Range)
Unit of measure:  Centimeters (cm)
Number Analyzed 31 participants
171.0
(147.0 to 189.0)
Weight  
Median (Full Range)
Unit of measure:  Kilograms (kg)
Number Analyzed 31 participants
68.0
(47.9 to 100.0)
1.Primary Outcome
Title Overview of Adverse Events
Hide Description Any untoward medical occurrence in a patient who received study drug was considered an adverse event (AE), without regard to possibility of causal relationship. Treatment-emergent adverse events (TEAE): those which occurred or worsened after baseline. An adverse event resulting in any of the following outcomes, or deemed to be significant for any other reason, was considered to be a serious adverse event (SAE): death; initial or prolonged inpatient hospitalization; a life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame baseline, up to 18 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who received at least one dose of study drug.
Arm/Group Title Pemetrexed
Hide Arm/Group Description:
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Overall Number of Participants Analyzed 31
Measure Type: Number
Unit of Measure: participants
TEAE - All, regardless of causality 28
TEAE - Possibly related to study drug 23
SAE - All, regardless of causality 12
SAE - Possibly related to study drug 1
Discontinuations Due to SAEs (including death) 4
Discontinuations - Possibly related to study drug 1
Discontinuations Due to Nonserious AEs 0
Deaths - On Study 2
Deaths - Possibly related to study drug 0
Deaths - Within 30 days of Study Discontinuation 0
2.Secondary Outcome
Title Number of Participants With Common Toxicity Criteria - National Cancer Institute Grade 3 and Grade 4 Toxicities
Hide Description

Number of participants with laboratory and non-laboratory toxicities possibly related to study drug, which were graded using the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) for defining and grading specific adverse events. Grades range from 0 (none) to 5 (death). Grade 3 is severe and Grade 4 is life-threatening.

NOS = Not otherwise specified.
Time Frame baseline, up to 18 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who received at least one dose of study drug.
Arm/Group Title Pemetrexed
Hide Arm/Group Description:
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Overall Number of Participants Analyzed 31
Measure Type: Number
Unit of Measure: participants
Leukocytopenia 1
Neutropenia/Granulocytopenia 1
Platelets 1
Ascites (Non-Malignant) 1
Febrile Neutropenia 1
Pain Pulmonary/Upper Respiratory-Chest/Thorax NOS 1
Pleural Effusion (Non-Malignant) 1
3.Secondary Outcome
Title Pemetrexed Population Pharmacokinetics (PK): Clearance
Hide Description Clearance (CL) can be defined as the volume of plasma which is completely cleared of drug (pemetrexed) per unit time. Total body clearance is calculated after intravenous administration of the drug (pemetrexed) and is measured by taking plasma samples at various timepoints and measuring the amount of pemetrexed in the plasma.
Time Frame Cycle 1 and Cycle 2: before the end of infusion (approximately 9.5 minutes), 2 hours, 9-10 hours, 24-48 hours, 480-528 hours (20 to 22 days) after start of pemetrexed infusion
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who received at least one dose of study drug.
Arm/Group Title Pemetrexed
Hide Arm/Group Description:
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Overall Number of Participants Analyzed 31
Mean (Standard Deviation)
Unit of Measure: milliliter per minute (mL/min)
85.6  (21.4)
4.Secondary Outcome
Title Pemetrexed Population Pharmacokinetics: Volume of Distribution
Hide Description Volume of distribution is the theoretical size of the compartment necessary to account for total drug amount in the body if it were present throughout the body in the same concentration found in plasma. Volume of distribution is defined as distribution of pemetrexed in the body and is determined by volume of distribution = dose/drug concentration. By knowing dose and measuring concentration of pemetrexed in plasma, volume was calculated. Central volume (V1) was determined by dose/peak serum level of pemetrexed. Peripheral volume (V2) is sum of all tissue spaces outside the central compartment.
Time Frame Cycle 1 and Cycle 2: before the end of infusion (approximately 9.5 minutes), 2 hours, 9-10 hours, 24-48 hours, 480-528 hours (20 to 22 days) after start of pemetrexed infusion
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who received at least one dose of study drug.
Arm/Group Title Pemetrexed
Hide Arm/Group Description:
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Overall Number of Participants Analyzed 31
Mean (Standard Deviation)
Unit of Measure: Liters (L)
Central Volume of Distribution 6.61  (1.32)
Peripheral Volume of Distribution (V2) 8.91  (1.68)
Peripheral Volume of Distribution (V3) 1.26  (0)
5.Secondary Outcome
Title Discontinuations Due to Adverse Events
Hide Description Adverse events were coded using the Medical Dictionary for Regulatory Activities, Version 11.0.
Time Frame baseline, up to 18 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who received at least one dose of study drug.
Arm/Group Title Pemetrexed
Hide Arm/Group Description:
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Overall Number of Participants Analyzed 31
Measure Type: Number
Unit of Measure: participants
Atrial fibrillation 1
Febrile neutropenia (possibly related) 1
Pneumonia (resulted in death) 1
Respiratory failure (resulted in death) 1
6.Other Pre-specified Outcome
Title Overall Tumor Response
Hide Description

Overall tumor response was determined using Response Evaluation Criteria In Solid Tumors (RECIST), which defines when cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progression") during treatments.

CR (complete response) = disappearance of all target lesions. PR (partial response) = 30% decrease in the sum of the longest diameter of target lesions.

PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions.

SD (stable disease) = small changes that do not meet above criteria.
Time Frame baseline, up to 18 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who received at least one dose of study drug.
Arm/Group Title Pemetrexed
Hide Arm/Group Description:
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Overall Number of Participants Analyzed 31
Measure Type: Number
Unit of Measure: participants
Complete Response 0
Partial Response 2
Stable Disease 8
Progressive Disease 12
Unknown 9
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Pemetrexed
Hide Arm/Group Description Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
All-Cause Mortality
Pemetrexed
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Pemetrexed
Affected / at Risk (%) # Events
Total   12/31 (38.71%)    
Blood and lymphatic system disorders   
Anaemia † 1  1/31 (3.23%)  1
Febrile neutropenia † 1  1/31 (3.23%)  1
Thrombocytopenia † 1  1/31 (3.23%)  1
Cardiac disorders   
Atrial fibrillation † 1  3/31 (9.68%)  3
Cardiac failure † 1  1/31 (3.23%)  1
Pericardial effusion † 1  1/31 (3.23%)  1
Gastrointestinal disorders   
Abdominal pain † 1  2/31 (6.45%)  2
Constipation † 1  1/31 (3.23%)  1
General disorders   
Pyrexia † 1  2/31 (6.45%)  3
Infections and infestations   
Infection † 1  1/31 (3.23%)  1
Pneumonia † 1  2/31 (6.45%)  2
Respiratory tract infection † 1  1/31 (3.23%)  1
Urinary tract infection † 1  1/31 (3.23%)  1
Respiratory, thoracic and mediastinal disorders   
Acute pulmonary oedema † 1  1/31 (3.23%)  1
Pleural effusion † 1  1/31 (3.23%)  1
Pneumothorax † 1  1/31 (3.23%)  1
Respiratory failure † 1  2/31 (6.45%)  2
Surgical and medical procedures   
Pericardial excision † 1  1/31 (3.23%)  1
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pemetrexed
Affected / at Risk (%) # Events
Total   28/31 (90.32%)    
Blood and lymphatic system disorders   
Anaemia † 1  5/31 (16.13%)  5
Lymphopenia † 1  2/31 (6.45%)  3
Neutropenia † 1  3/31 (9.68%)  4
Gastrointestinal disorders   
Abdominal pain upper † 1  2/31 (6.45%)  3
Constipation † 1  7/31 (22.58%)  8
Diarrhoea † 1  4/31 (12.90%)  4
Nausea † 1  10/31 (32.26%)  11
Vomiting † 1  3/31 (9.68%)  4
General disorders   
Asthenia † 1  8/31 (25.81%)  11
Chest pain † 1  2/31 (6.45%)  2
Fatigue † 1  9/31 (29.03%)  13
Influenza like illness † 1  2/31 (6.45%)  2
Mucosal inflammation † 1  3/31 (9.68%)  4
Oedema peripheral † 1  5/31 (16.13%)  5
Pain † 1  2/31 (6.45%)  2
Pyrexia † 1  3/31 (9.68%)  9
Infections and infestations   
Respiratory tract infection † 1  4/31 (12.90%)  4
Metabolism and nutrition disorders   
Anorexia † 1  7/31 (22.58%)  7
Musculoskeletal and connective tissue disorders   
Back pain † 1  4/31 (12.90%)  4
Muscular weakness † 1  2/31 (6.45%)  2
Musculoskeletal pain † 1  2/31 (6.45%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Tumour pain † 1  2/31 (6.45%)  2
Nervous system disorders   
Dizziness † 1  5/31 (16.13%)  5
Headache † 1  2/31 (6.45%)  2
Paraesthesia † 1  2/31 (6.45%)  2
Peripheral sensory neuropathy † 1  2/31 (6.45%)  3
Respiratory, thoracic and mediastinal disorders   
Cough † 1  5/31 (16.13%)  6
Dyspnoea † 1  5/31 (16.13%)  5
Productive cough † 1  3/31 (9.68%)  3
Skin and subcutaneous tissue disorders   
Dermatitis acneiform † 1  2/31 (6.45%)  2
Pruritus † 1  3/31 (9.68%)  4
Rash † 1  2/31 (6.45%)  2
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
[Not Specified]
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00316225    
Other Study ID Numbers: 10426
H3E-MC-JMHX ( Other Identifier: Eli Lilly and Company )
First Submitted: April 18, 2006
First Posted: April 20, 2006
Results First Submitted: March 10, 2010
Results First Posted: July 9, 2010
Last Update Posted: July 9, 2010