Pemetrexed Disodium in Treating Patients With Stage IV Non-small Cell Lung Cancer and ECOG Performance Status 3

Study Overview
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Brief Summary
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This pilot phase II trial studies how well pemetrexed disodium works in treating patients with stage IV non-small cell lung cancer and an Eastern Cooperative Oncology Group (ECOG) performance status of 3. Performance status means how well patients are able to perform daily activities and care for themselves. Patients with a performance status of 3 have a limited ability to move around. Currently, only patients who are able to perform most of their daily activities may receive chemotherapy, due to the side effects it may cause. Pemetrexed disodium causes fewer side effects than many chemotherapy drugs and may help treat patients with stage IV non-small cell lung cancer and a lower performance status.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the effect of single agent pemetrexed (pemetrexed disodium) on tumor progression in ECOG performance status 3 patients with stage IV non-squamous histology non-small cell lung cancer in a single arm pilot study. II. To evaluate the effect of single agent pemetrexed on quality of life in ECOG performance status 3 patients with stage IV non-squamous histology non-small cell lung cancer in a single arm pilot study. SECONDARY OBJECTIVES: I. To evaluate toxicity associated with single agent pemetrexed on tumor progression in ECOG performance status 3 patients with stage IV non-squamous histology non-small cell lung cancer in a single arm pilot study. OUTLINE: Patients receive pemetrexed disodium intravenously (IV) over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for at least 30 days and then every 6 weeks thereafter.

Official Title
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A Pilot Study Evaluating Pemetrexed in ECOG Performance Status 3 Patients With Stage IV Non-squamous Non-small Cell Lung Cancer

Conditions
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Stage IV Non-Small Cell Lung Cancer

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Drug: Pemetrexed Disodium
* Other: Quality-of-Life Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically confirmed Stage IV non-squamous histology non-small cell lung cancer ECOG performance status of 3 Sensitizing epidermal growth factor receptor (EGFR), anaplastic lymphoma receptor tyrosine kinase (ALK) and ROS proto-oncogene 1, receptor tyrosine kinase (ROS-1) mutations are either negative or unknown Absolute neutrophil count >= 1,500/mcL Platelets >= 100,000/mcL Creatinine clearance >= 45 mL/min Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document Ability to understand and complete the European Organization for Research and Treatment of Cancer (EORTC) quality of life (QOL) instruments Exclusion Criteria: Patients who have previously received chemotherapy for non-small cell lung cancer, or have received radiotherapy within 2 weeks prior to entering the study, or who have not recovered from adverse events due to treatment more than 2 weeks earlier Patients whose tumors are positive for the sensitizing EGFR mutation Patients whose tumors are positive for the sensitizing ALK fusion Patients whose tumors are positive for the sensitizing ROS-1 fusion Patients may not be receiving any other investigational agents Patients with symptomatic or recurrent brain metastases should be excluded from this clinical trial History of allergic reactions attributed to compounds of similar chemical or biologic composition to pemetrexed Pregnant women are excluded from this study; breastfeeding should be discontinued

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (pemetrexed disodium)<br>Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Quality-of-Life Assessment and Laboratory Biomarker Analysis. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Pemetrexed Disodium<br>* Given IV<br>* Other names: N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt;Other: Quality-of-Life Assessment<br>* QOL studies<br>* Other names: Quality of Life Assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quality of Life (QOL), Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) and QLQ-Lung Cancer 13-item (LC13) | Quality of life will be assessed at each treatment time (i.e. every three weeks). A longitudinal mixed models analysis will be used to look at QOL over the time course. A paired t-test will also be calculated to see if the average change is more than 0 (worsening) versus a two-sided alternative that the difference is 0 or better. Score range from 0-100 (1 = not at all, 2 = a little, 3 = quite a bit, or 4 = very much). The higher the score, the greater the change in the quality of life for the worse. | Baseline to 12 weeks | 
| Time to Tumor Progression | It will be determined whether each patient has a progression (or dies) before or after 12 weeks. A 95% exact (Clopper Pearson) confidence interval will then be around the proportion with PFS greater than or equal to 12 weeks. If this confidence interval includes 50% then that would provide evidence that the therapy is potentially promising. If the upper bound of the confidence interval does not include 50% then this would indicate that the treatment may not be promising for patients. In addition, a Kaplan Meier survival curve will be constructed to describe the time to progression data. | The duration of time from the start of treatment to the time of progression, death, or date of last contact, assessed up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Hematologic Toxicity, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 | The number and type of toxicities observed during this protocol will be estimated, focusing on unexpected grade 3 or higher toxicities. No formal statistical tests will be done on these estimates. | Up to 30 days | 
| Overall Survival | Examined by estimating a Kaplan-Meier survival curve using all patients enrolled. | The duration of time from the start of treatment to date of death or date of last contact, assessed up to 2 years | 
| Response Rate | Response rate will be estimated every 6 weeks for patients, and these estimates will be presented with confidence intervals. | Up to 2 years |