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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00316225

Enrollment

Registered

2006-04-20

Start date

2006-12-31

Completion date

2009-03-31

Last updated

2010-07-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lung Neoplasms, Mesothelioma, Non-small Cell Lung Cancer

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.

Interventions

DRUGpemetrexed

500 milligrams per meter squared (mg/m\^2) IV every 21 days for 6 cycles

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Overview of Adverse Events	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

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

Other

Measure	Time frame	Description
Overall Tumor Response	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.

Countries

Denmark, Germany, Spain

Participant flow

Participants by arm

Arm	Count
Pemetrexed Pemetrexed 500 mg/m2 intravenous (IV) every 21 days for 6 cycles	31
Total	31

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	2
Overall Study	Death	2
Overall Study	Physician Decision	3
Overall Study	Progressive Disease	15
Overall Study	Withdrawal by Subject	3

Baseline characteristics

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

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	28 / 31
serious Total, serious adverse events	12 / 31

Outcome results

Primary

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.

Time frame: baseline, up to 18 weeks