The aim of this study is to compare time to progression between the combination pemetrexed-carboplatin and pemetrexed alone in previously treated patients with locally advanced or metastatic NSCLC.

In spite of the superiority of single agent over best supportive care in second-line NSCLC, the prognosis of these patients remains poor with a median survival of 6-7 months, justifying the evaluation of new regimens in this setting. An open question in the second-line treatment of NSCLC remains the possible superiority of combination chemotherapy over single agent, as it has been clearly demonstrated in first-line. Particularly, the addition of platinum to either docetaxel or pemetrexed should be further investigated especially in patients with prior response/stable disease to platinum-based first-line chemotherapy. Pemetrexed has shown anti-tumor activity in combination with other chemotherapy agents, including gemcitabine, vinorelbine, taxanes, cisplatin and carboplatin. In this multicenter, open label, randomized phase II trial, pemetrexed 500 mg/m2 and carboplatin AUC 5 will be administered on day 1 every 3 weeks until progression of disease or for a maximum of 4 courses in the experimental arm. The control arm will be pemetrexed as single agent at 500 mg/m2 on day 1 every 3 weeks until progression of disease or for a maximum of 4 courses.

Inclusion Criteria:

• written informed consent
• Histologically or cytologically confirmed non-small-cell lung cancer
• Unresectable stage IIIB, stage IV and unresectable local relapse or metastatic disease, with evidence of disease progression after first line chemotherapy which should have included a platinum agent.
• ECOG performance status lower than or equal to 2
• Adequate hematological, hepatic and renal functions
• Life expectancy greater than or equal to 12 weeks
• Prior treatment with only 1 chemotherapy regimen for the treatment of advanced disease which should have included a platinum agent
• At baseline, presence of at least one measurable target lesion as per RECIST criteria

Exclusion Criteria:

• Prior treatment with pemetrexed.
• Patients who are pregnant or lactating
• Patients with any underlying medical condition that might be aggravated by treatment or which cannot be controlled.
• Symptomatic brain metastases
• History of another malignancy within the past five years except basal cell carcinoma of the skin or carcinoma in situ of the cervix.
• Concomitant treatment with any other anticancer drug.