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

Study Overview
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Brief Summary
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This study will test the effects of pemetrexed on mesothelioma and non-small cell lung cancer patients with fluid around their lungs or abdomen.

Official Title
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A Phase 2 Study of ALIMTA in Solid Tumor Patients With Stable Third-Space Fluid

Conditions
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Non-small Cell Lung Cancer, Mesothelioma, Lung Neoplasms

Intervention / Treatment
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* Drug: pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of locally advanced or metastatic (Stage III or IV at entry) non-small cell lung cancer (NSCLC) or mesothelioma Presence of third-space fluid (fluid around the lungs or abdomen). Eastern Cooperative Oncology Group Performance Status of 0 or 1. Prior anticancer treatment (except radiation) must be completed at least 3 weeks prior to study enrollment, and the patient must have recovered from the sharp toxic effects the anticancer treatment. Estimated life expectancy of at least 8 weeks. Exclusion Criteria: Have received treatment within the last 30 days with a drug that was not a marketed product. Active infection that, in the opinion of the investigator, would not allow the patient to tolerate therapy. Pregnancy. Breast-feeding. Significant weight loss (that is, greater than or equal to 10% of body weight) over the 6 weeks before study entry. Brain metastases.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemetrexed<br>Pemetrexed 500 mg/m^2 intravenous (IV) every 21 days for 6 cycles | Drug: pemetrexed<br>* 500 milligrams per meter squared (mg/m^2) IV every 21 days for 6 cycles<br>* Other names: Alimta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overview of Adverse Events | 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. | baseline, up to 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Common Toxicity Criteria - National Cancer Institute Grade 3 and Grade 4 Toxicities | 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. | baseline, up to 18 weeks | 
| Pemetrexed Population Pharmacokinetics (PK): Clearance | 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. | 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 | 
| Pemetrexed Population Pharmacokinetics: Volume of Distribution | 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. | 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 | 
| Discontinuations Due to Adverse Events | Adverse events were coded using the Medical Dictionary for Regulatory Activities, Version 11.0. | baseline, up to 18 weeks |