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

• 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: Eli Lilly and Company
• Information provided by: Eli Lilly and Company

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer; Mesothelioma; Lung Neoplasms	Drug: pemetrexed	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of ALIMTA in Solid Tumor Patients With Stable Third-Space Fluid
• Study Start Date: December 2006
• Actual Primary Completion Date: March 2009
• Actual Study Completion Date: March 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pemetrexed; Pemetrexed 500 mg/m^2 intravenous (IV) every 21 days for 6 cycles	Drug: pemetrexed; 500 milligrams per meter squared (mg/m^2) IV every 21 days for 6 cycles; Other Names: LY231514; Alimta

Outcome Measures

Primary Outcome Measures :

1. Overview of Adverse Events [ Time Frame: baseline, up to 18 weeks ]
   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.

Secondary Outcome Measures :

1. Number of Participants With Common Toxicity Criteria - National Cancer Institute Grade 3 and Grade 4 Toxicities [ Time Frame: baseline, up to 18 weeks ]

   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.

2. Pemetrexed Population Pharmacokinetics (PK): Clearance [ 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 ]
   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.
3. Pemetrexed Population Pharmacokinetics: Volume of Distribution [ 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 ]
   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.
4. Discontinuations Due to Adverse Events [ Time Frame: baseline, up to 18 weeks ]
   Adverse events were coded using the Medical Dictionary for Regulatory Activities, Version 11.0.

Other Outcome Measures:

1. Overall Tumor Response [ Time Frame: baseline, up to 18 weeks ]

   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Denmark

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Kobenhavn, Denmark, 2100

Germany

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Hannover, Germany, 30625

Spain

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Madrid, Spain, 28041

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

Additional Information:

Lilly Clinical Trial Registry 

• 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 Posted: April 20, 2006
• Results First Posted: July 9, 2010
• Last Update Posted: July 9, 2010
• Last Verified: June 2010

Additional relevant MeSH terms:

Lung Neoplasms; Mesothelioma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Mesothelial; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors