Trial Outcomes & Findings for Study of Pemetrexed in Mesothelioma and Lung Cancer Patients With Fluid Around the Lungs or Abdomen (NCT NCT00316225)

NCT ID: NCT00316225

Last Updated: 2010-07-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

baseline, up to 18 weeks

Results posted on

2010-07-09

Participant Flow

Participant milestones

Participant milestones
Measure
Pemetrexed
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Overall Study
STARTED
31
Overall Study
COMPLETED
6
Overall Study
NOT COMPLETED
25

Reasons for withdrawal

Reasons for withdrawal
Measure
Pemetrexed
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Overall Study
Adverse Event
2
Overall Study
Physician Decision
3
Overall Study
Progressive Disease
15
Overall Study
Withdrawal by Subject
3
Overall Study
Death
2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Pemetrexed
n=31 Participants
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Age Continuous
62.7 years
n=5 Participants
Sex: Female, Male
Female
4 Participants
n=5 Participants
Sex: Female, Male
Male
27 Participants
n=5 Participants
Race/Ethnicity, Customized
Caucasian
30 participants
n=5 Participants
Race/Ethnicity, Customized
Hispanic
1 participants
n=5 Participants
Region of Enrollment
Spain
12 participants
n=5 Participants
Region of Enrollment
Denmark
6 participants
n=5 Participants
Region of Enrollment
Germany
13 participants
n=5 Participants
Diagnosis
Non-Small Cell Lung Cancer (NSCLC)
23 participants
n=5 Participants
Diagnosis
Mesothelioma
8 participants
n=5 Participants
Disease Stage
Stage III (locally advanced disease)
12 participants
n=5 Participants
Disease Stage
Stage IV (metastatic disease)
18 participants
n=5 Participants
Disease Stage
Unknown
1 participants
n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status
0 - Fully Active
14 participants
n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status
1 - Ambulatory, Restricted Strenuous Activity
17 participants
n=5 Participants
Fluid Severity
Mild
15 participants
n=5 Participants
Fluid Severity
Moderate
14 participants
n=5 Participants
Fluid Severity
Severe
2 participants
n=5 Participants
Primary Basis for Diagnosis
Cytological
6 participants
n=5 Participants
Primary Basis for Diagnosis
Histopathological
25 participants
n=5 Participants
Type of Third-Space Fluid
Pleural Effusion
30 participants
n=5 Participants
Type of Third-Space Fluid
Ascites
1 participants
n=5 Participants
Body Surface Area
1.8 meters squared (m^2)
n=5 Participants
Height
171.0 centimeters (cm)
n=5 Participants
Weight
68.0 kilograms (kg)
n=5 Participants

PRIMARY outcome

Timeframe: baseline, up to 18 weeks

Population: Patients who received at least one dose of study drug.

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.

Outcome measures

Outcome measures
Measure
Pemetrexed
n=31 Participants
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Overview of Adverse Events
TEAE - Possibly related to study drug
23 participants
Overview of Adverse Events
TEAE - All, regardless of causality
28 participants
Overview of Adverse Events
SAE - All, regardless of causality
12 participants
Overview of Adverse Events
SAE - Possibly related to study drug
1 participants
Overview of Adverse Events
Discontinuations Due to SAEs (including death)
4 participants
Overview of Adverse Events
Discontinuations - Possibly related to study drug
1 participants
Overview of Adverse Events
Discontinuations Due to Nonserious AEs
0 participants
Overview of Adverse Events
Deaths - On Study
2 participants
Overview of Adverse Events
Deaths - Possibly related to study drug
0 participants
Overview of Adverse Events
Deaths - Within 30 days of Study Discontinuation
0 participants

SECONDARY outcome

Timeframe: baseline, up to 18 weeks

Population: Patients who received at least one dose of study drug.

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.

Outcome measures

Outcome measures
Measure
Pemetrexed
n=31 Participants
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Number of Participants With Common Toxicity Criteria - National Cancer Institute Grade 3 and Grade 4 Toxicities
Pleural Effusion (Non-Malignant)
1 participants
Number of Participants With Common Toxicity Criteria - National Cancer Institute Grade 3 and Grade 4 Toxicities
Leukocytopenia
1 participants
Number of Participants With Common Toxicity Criteria - National Cancer Institute Grade 3 and Grade 4 Toxicities
Neutropenia/Granulocytopenia
1 participants
Number of Participants With Common Toxicity Criteria - National Cancer Institute Grade 3 and Grade 4 Toxicities
Platelets
1 participants
Number of Participants With Common Toxicity Criteria - National Cancer Institute Grade 3 and Grade 4 Toxicities
Ascites (Non-Malignant)
1 participants
Number of Participants With Common Toxicity Criteria - National Cancer Institute Grade 3 and Grade 4 Toxicities
Febrile Neutropenia
1 participants
Number of Participants With Common Toxicity Criteria - National Cancer Institute Grade 3 and Grade 4 Toxicities
Pain Pulmonary/Upper Respiratory-Chest/Thorax NOS
1 participants

SECONDARY outcome

Timeframe: 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

Population: Patients who received at least one dose of study drug.

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.

Outcome measures

Outcome measures
Measure
Pemetrexed
n=31 Participants
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Pemetrexed Population Pharmacokinetics (PK): Clearance
85.6 milliliter per minute (mL/min)
Standard Deviation 21.4

SECONDARY outcome

Timeframe: 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

Population: Patients who received at least one dose of study drug.

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.

Outcome measures

Outcome measures
Measure
Pemetrexed
n=31 Participants
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Pemetrexed Population Pharmacokinetics: Volume of Distribution
Central Volume of Distribution
6.61 Liters (L)
Standard Deviation 1.32
Pemetrexed Population Pharmacokinetics: Volume of Distribution
Peripheral Volume of Distribution (V2)
8.91 Liters (L)
Standard Deviation 1.68
Pemetrexed Population Pharmacokinetics: Volume of Distribution
Peripheral Volume of Distribution (V3)
1.26 Liters (L)
Standard Deviation 0

SECONDARY outcome

Timeframe: baseline, up to 18 weeks

Population: Patients who received at least one dose of study drug.

Adverse events were coded using the Medical Dictionary for Regulatory Activities, Version 11.0.

Outcome measures

Outcome measures
Measure
Pemetrexed
n=31 Participants
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Discontinuations Due to Adverse Events
Febrile neutropenia (possibly related)
1 participants
Discontinuations Due to Adverse Events
Pneumonia (resulted in death)
1 participants
Discontinuations Due to Adverse Events
Atrial fibrillation
1 participants
Discontinuations Due to Adverse Events
Respiratory failure (resulted in death)
1 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline, up to 18 weeks

Population: Patients who received at least one dose of study drug.

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.

Outcome measures

Outcome measures
Measure
Pemetrexed
n=31 Participants
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Overall Tumor Response
Complete Response
0 participants
Overall Tumor Response
Partial Response
2 participants
Overall Tumor Response
Stable Disease
8 participants
Overall Tumor Response
Progressive Disease
12 participants
Overall Tumor Response
Unknown
9 participants

Adverse Events

Pemetrexed

Serious events: 12 serious events
Other events: 28 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Pemetrexed
n=31 participants at risk
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Blood and lymphatic system disorders
Anaemia
3.2%
1/31 • Number of events 1
Blood and lymphatic system disorders
Febrile neutropenia
3.2%
1/31 • Number of events 1
Blood and lymphatic system disorders
Thrombocytopenia
3.2%
1/31 • Number of events 1
Cardiac disorders
Atrial fibrillation
9.7%
3/31 • Number of events 3
Cardiac disorders
Cardiac failure
3.2%
1/31 • Number of events 1
Cardiac disorders
Pericardial effusion
3.2%
1/31 • Number of events 1
Gastrointestinal disorders
Abdominal pain
6.5%
2/31 • Number of events 2
Gastrointestinal disorders
Constipation
3.2%
1/31 • Number of events 1
General disorders
Pyrexia
6.5%
2/31 • Number of events 3
Infections and infestations
Infection
3.2%
1/31 • Number of events 1
Infections and infestations
Pneumonia
6.5%
2/31 • Number of events 2
Infections and infestations
Respiratory tract infection
3.2%
1/31 • Number of events 1
Infections and infestations
Urinary tract infection
3.2%
1/31 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
3.2%
1/31 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Pleural effusion
3.2%
1/31 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Pneumothorax
3.2%
1/31 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Respiratory failure
6.5%
2/31 • Number of events 2
Surgical and medical procedures
Pericardial excision
3.2%
1/31 • Number of events 1

Other adverse events

Other adverse events
Measure
Pemetrexed
n=31 participants at risk
Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles
Blood and lymphatic system disorders
Anaemia
16.1%
5/31 • Number of events 5
Blood and lymphatic system disorders
Lymphopenia
6.5%
2/31 • Number of events 3
Blood and lymphatic system disorders
Neutropenia
9.7%
3/31 • Number of events 4
Gastrointestinal disorders
Abdominal pain upper
6.5%
2/31 • Number of events 3
Gastrointestinal disorders
Constipation
22.6%
7/31 • Number of events 8
Gastrointestinal disorders
Diarrhoea
12.9%
4/31 • Number of events 4
Gastrointestinal disorders
Nausea
32.3%
10/31 • Number of events 11
Gastrointestinal disorders
Vomiting
9.7%
3/31 • Number of events 4
General disorders
Asthenia
25.8%
8/31 • Number of events 11
General disorders
Chest pain
6.5%
2/31 • Number of events 2
General disorders
Fatigue
29.0%
9/31 • Number of events 13
General disorders
Influenza like illness
6.5%
2/31 • Number of events 2
General disorders
Mucosal inflammation
9.7%
3/31 • Number of events 4
General disorders
Oedema peripheral
16.1%
5/31 • Number of events 5
General disorders
Pain
6.5%
2/31 • Number of events 2
General disorders
Pyrexia
9.7%
3/31 • Number of events 9
Infections and infestations
Respiratory tract infection
12.9%
4/31 • Number of events 4
Metabolism and nutrition disorders
Anorexia
22.6%
7/31 • Number of events 7
Musculoskeletal and connective tissue disorders
Back pain
12.9%
4/31 • Number of events 4
Musculoskeletal and connective tissue disorders
Muscular weakness
6.5%
2/31 • Number of events 2
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
6.5%
2/31 • Number of events 2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
6.5%
2/31 • Number of events 2
Nervous system disorders
Dizziness
16.1%
5/31 • Number of events 5
Nervous system disorders
Headache
6.5%
2/31 • Number of events 2
Nervous system disorders
Paraesthesia
6.5%
2/31 • Number of events 2
Nervous system disorders
Peripheral sensory neuropathy
6.5%
2/31 • Number of events 3
Respiratory, thoracic and mediastinal disorders
Cough
16.1%
5/31 • Number of events 6
Respiratory, thoracic and mediastinal disorders
Dyspnoea
16.1%
5/31 • Number of events 5
Respiratory, thoracic and mediastinal disorders
Productive cough
9.7%
3/31 • Number of events 3
Skin and subcutaneous tissue disorders
Dermatitis acneiform
6.5%
2/31 • Number of events 2
Skin and subcutaneous tissue disorders
Pruritus
9.7%
3/31 • Number of events 4
Skin and subcutaneous tissue disorders
Rash
6.5%
2/31 • Number of events 2

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: GT60