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

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.

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