NCT01656551.

Trial name or title	A Factorial Study Comparing Pemetrexed With Gemcitabine and Testing the Efficacy of the Addition of Cisplatin in Elderly Patients With Non‐Squamous Advanced, Metastatic, or Recurrent NSCLC
Methods	Controlled randomized trial, open‐label, multi‐center. This study used a factorial design that allowed 2 comparisons: single‐agent therapy vs chemotherapy plus cisplatin (arms A + C vs arms B + D), and gemcitabine vs pemetrexed (arms A + B vs arms C + D)
Participants	Eligibility criteria Inclusion criteria Diagnosis of cytologically or histologically confirmed non‐small cell lung cancer Non‐squamous tumor type (including those with a non‐specified tumor type) Metastatic (stage IV, both M1A or M1B) or locally advanced (stage IIIB, with metastasis to supraclavicular nodes), according to TNM VII edition First diagnosis or disease recurrence after former surgery ≥ 1 target or non‐target lesion according to Response Evaluation Criteria in Solid Tumor (RECIST) revised version 1.1 Male or female ≥ 70 years of age Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0 or 1 Life expectancy > 3 months Neutrophils ≥ 1500 mm3, platelets ≥ 100,000 mm3, and hemoglobin ≥ 9 g/dL Bilirubin level normal or < 1.5 × upper limit of normal (ULN) Aspartate amino transferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 2.5 × ULN (≤ 5 × ULN if liver metastasis present) Serum creatinine < 1.5 × ULN Signed written informed consent Exclusion criteria Prior chemotherapy or systemic anti‐neoplastic therapy for advanced disease ‐ prior surgery and/or localized irradiation permitted. Prior adjuvant chemotherapy permitted if it did not contain gemcitabine and pemetrexed, and if ≥ 6 months had elapsed from end of adjuvant chemotherapy Unstable systemic disease (including active infection; significant cardiovascular disease or myocardial infarction within previous year; significant hepatic, renal, or metabolic disease), metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates use of study medications or renders patient at high risk from treatment complications Other malignancy within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer or surgically resected prostate cancer with normal prostate‐specific antigen (PSA)) Symptomatic brain metastasis or spinal cord compression not yet treated with surgery and/or radiation; central nervous system (CNS) metastasis or spinal cord compression previously treated with surgery and/or radiation if asymptomatic and not requiring steroids (anti‐seizure medications allowed) Known or suspected hypersensitivity to any study drug
Interventions	Arm A (active comparator): gemcitabine 1200 mg/m2 days 1 and 8, every 3 weeks Arm B (experimental arm): cisplatin 60 mg/m2 day 1 + gemcitabine 1000 mg/m2 days 1 and 8, every 3 weeks Arm C (active comparator): pemetrexed 500 mg/m2 i.v. day 1, every 3 weeks Arm D (experimental arm): cisplatin 60 mg/m2 day 1 + pemetrexed 500 mg/m2 day 1, every 3 weeks
Outcomes	Primary outcome Overall survival Secondary outcomes Worst grade toxicity per participant according to Common Toxicity Criteria for Adverse Events v. 4.03 Progression‐free survival Changes in quality of life Objective response Other outcome measures Identification of participant and lesion‐specific prognostic factors Identification of participant and lesion‐specific factors predictive of chemotherapy efficacy
Starting date	July 2012
Contact information	Francesco Perrone, M.D., Ph.D.; +39 081 5903571; email: francesco.perrone@usc‐intnapoli.net Maria Carmela Piccirillo, M.D.; +39 081 5903681; email: marilina.piccirillo@usc‐intnapoli.net
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