PS2Phase III Trial of Single-Agent Pemetrexed (Alimta®) Versus the Combination of Carboplatin and Pemetrexed in Patients With Advanced Non-small-cell Lung Cancer and Performance Status of 2

Study start date: April 1, 2008

Inclusion Criteria: Newly diagnosed NSCLC in stage IIIB (with a cytologically positive pleural or pericardial effusion) or stage IV, according to the sixth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual37; Age > 18 years; No prior chemotherapy, including adjuvant or neoadjuvant therapy, for the treatment of NSCLC; Histological confirmation of any non-squamous histological type of NSCLC, given the recent findings of treatment benefit in this population44; ECOG performance status of 2; At least 3 weeks must have elapsed since major surgery, and at least 1 week since mediastinoscopy, pleuroscopy, or thoracostomy; Patients must have measurable disease, defined as lesions that can be accurately measured in at least 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques (computed tomography [CT] or magnetic resonance imaging [MRI] scan) or as ≥ 10 mm with spiral CT scan; Adequate organ function as indicated by the following: White blood cell (WBC) count ≥ 3500/mm3 Absolute neutrophil count (ANC) ≥1500/mm3 Hemoglobin ≥ 9.0 g/dL Platelet count ≥ 100,000/ mm3 Total bilirubin ≤ 2 times the upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the ULN, unless liver metastases present, in which case AST and ALT have to be ≤ 5 times the ULN Estimated glomerular filtration rate (GFR) ≥ 45 mL/min Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration; Fertile patients (male or female) must agree to use an acceptable method of contraception to avoid pregnancy for the duration of the study and for 3 months thereafter; Patients must sign an Informed Consent Form; Have the ability to take folic acid, Vitamin B12, and dexamethasone according to protocol requirements; Exclusion Criteria: ECOG performance status other than 2; Prior chemotherapy for the treatment of NSCLC; Lesions that have been irradiated cannot be included as sites of measurable disease. If the only measurable lesion was previously irradiated the patient cannot be included; Symptomatic central nervous system (CNS) metastases. Prior CNS metastases are allowed if the patient is neurologically stable and not receiving corticosteroids; Serious uncontrolled intercurrent medical or psychiatric illness; Active and ongoing systemic infection; Second primary malignancy (except in situ carcinoma of the cervix, in situ carcinoma of the bladder, adequately treated basal-cell carcinoma of the skin, adequately treated squamous-cell carcinoma of the skin, T1 vocal cord cancer in remission, or prior malignancy treated more than 5 years prior to enrollment and without recurrence); Known hypersensitivity to pemetrexed; known hypersensitivity to carboplatin; Pregnancy or lactation; Use of any investigational agent within 30 days prior to enrollment into the study; Unable to discontinue administration of non-steroidal anti-inflammatory (NSAIDSs) agents for 2 days before, the day of and 2 days after the dose of pemetrexed, in the case of NSAIDs with short half-life, such as ibuprofen (total of 5 days), in patients with a GFR between 45 and 79 mL/min; and for 5 days before, the day of and 2 days after the dose of pemetrexed, in the case of NSAIDs with long half-life (total of 8 days, see 7.4.2) in all patients; patients with a GFR ≥ 80 mL/min may receive concomitant study treatment and ibuprofen or aspirin (≤ 1.3 g/day); Inability to comply with requirements and procedures of study.