An open-label phase I-II trial will be performed in 42 patients with pretreated locally advanced non-small cell lung cancer. The trial is designed to estimate the efficacy and to determine safety of NovoTTF-100L treatment combined with Pemetrexed for advanced NSCLC patients. Patients will receive standard Pemetrexed therapy (at 500 mg/m2 iv q3w for 3 cycles) concomitant to NovoTTF-100L therapy (12 hours a day, daily until the end of all three cycles of Alimta). Repeat treatments with Alimta + NovoTTF-100L will be offered as long as the patient is stable or responding. If there is a in-field response with progression outside of the NovoTTF field, Pemetrexed is to be stopped and third line chemotherapy with Docetaxel is to be initiated (35 mg/m2 weekly, d1, 8, 15, q 28 d).

The trial will be conducted in two stages. Fourteen patients will be recruited to a phase I stage of the trial. After all 14 patients have received 3 courses of Alimta (9 weeks of NovoTTF-100L treatment), these patients will be analyzed for toxicity. If the incidence of device related serious adverse events is < 20%, the trial will continue to the second stage where 42 patients will be assessed for safety and efficacy as part of a phase II study (including the first 14 patients in the phase I study).

Efficacy will be assessed based on local disease control in the lungs and liver, time to systemic disease progression, and overall survival. Patients will be followed for at least 6 months after the last course of NovoTTF-100L is applied to assess survival.

Inclusion Criteria:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
• Stage IV or IIIB with malignant pleural effusion, also locally advanced NSCLC not otherwise amenable to local treatment (surgery or radiotherapy)
• One line of prior chemotherapy
• Measurable disease
• Greater or equal to 18 years
• Life expectancy of at least 12 weeks
• ECOG performance status 0-2
• Laboratory requirements at entry:
• Blood cell counts:
• Absolute neutrophils ≥ 1.0 x 109/L
• Platelets ≥100 x 109/L
• Hemoglobin ≥ 10 g/dl
• Renal function:
• Creatinine clearance ≥ 45 mL/min
• Hepatic functions:
• ASAT and ALAT ≤ 3 x UNL
• Alkaline phosphatase ≤ 5 x UNL
• Signed informed consent prior to start protocol specific requirements
• Pregnancy test (β-HCG) must be negative (needed only for women of childbearing potential).

Exclusion Criteria:

• Known brain metastases or meningeal carcinomatosis
• Other serious concomitant illness of medical conditions:
• Congestive heart failure or angina pectoris except if it is medically controlled.
• Previous history of myocardial infarction within 1 year from study entry.
• Uncontrolled hypertension or arrhythmias
• Implanted pacemaker, defibrillator or deep brain stimulation device
• History of significant neurologic or psychiatric disorders including dementia or seizures
• Active infection requiring iv antibiotics
• Active ulcer, unstable diabetes mellitus or other contra-indication to corticosteroid therapy
• Concurrent treatment with other experimental drugs
• Participation in clinical trials with other experimental agents within 30 days of study entry
• Psychological, familial, sociological or geographical conditions which don't permit medical follow-up and compliance with the study protocol