A Phase I/II Study of Paclitaxel, Carboplatin and YM155 (Survivin Suppressor) in Subjects With Solid Tumors (Phase I) and Advanced Non-Small Cell Lung Carcinoma (Phase II)

Background: * Treatment with platinum-based doublet chemotherapy results in a median survival of 7 to 10 months in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). * Carboplatin-paclitaxel is a commonly used regimen in advanced NSCLC and other solid tumors. In a randomized clinical trial carboplatin, paclitaxel plus bevacizumab resulted in improved efficacy (response rate and survival) compared to carboplatin and paclitaxel alone but only patients with non-squamous histology and who were considered low risk of bleeding were treated. Improvement of survival was not confirmed in another randomized study with a different chemotherapy backbone. * Novel treatment strategies need to be developed for advanced NSCLC. * YM155 is a transcriptional inhibitor of survivin, an inhibitor of apoptosis protein. Pre-clinical activity of YM155 has been observed in several solid tumors, including NSCLC models and synergy was observed in combination with chemotherapeutic drugs, including carboplatin and paclitaxel. * YM155 has been investigated in several phase I and phase II clinical trials and it has been shown to be well tolerated with the most common toxicities reported as being reversible and of grades 1 -2 in severity. In addition, as a monotherapy YM155 alone has shown modest antitumor activity in a phase II trial in advanced NSCLC in patients who had failed one or two prior chemotherapy lines. Primary Objectives: * In the Phase I portion of the study the primary objective will be to determine a safe and tolerable phase II dose of YM155 based upon dose limiting toxicities (DLTs) when YM155 is administered over 72 hours by continuous intravenous infusion (CIVI) every 3 weeks in combination with paclitaxel and carboplatin. * In the Phase II portion of the study the primary objective will be to determine the objective response rate (ORR = partial response (PR)+ complete response (CR)) of YM155 in combination with carboplatin and paclitaxel in the first line treatment of patients with advanced NSCLC. Secondary Objectives: * In the Phase I portion of the study the secondary objective will be to determine the preliminary activity of the combination regimen based upon response rate as measured by response evaluation criteria in solid tumors \[RECIST\]. * In the Phase II portion of the study the secondary objectives will be to determine the median progression free survival (PFS), median overall survival (OS) and safety and tolerability of this combination regimen in this patient population. * To assess expression of particular genes on the pretreatment tumor and pre/post treatment serum samples to evaluate the treatment effects and correlate them with clinical outcome. Eligibility: Phase I \- The phase I portion of the trial will be open to all patients with recurrent or advanced cancer (NSCLC and other solid tumors) for whom standard therapy offers no curative potential and also in patients for whom the carboplatin / paclitaxel regimen is considered standard of care. Patients should have received no more than one previous chemotherapy regimen. Phase II * Pathologically confirmed stage IIIB (malignant pleural effusion) or intravenous (IV) or recurrent NSCLC. * No previous chemotherapy for advanced lung cancer. * Adequate organ and bone marrow function. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Design: * Open label phase I/II trial * Following a Simon two-stage optimal design