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)

INCLUSION CRITERIA:

Response should be YES

Phase 1 and 2:

Has a signed consent/assent been obtained by the patient or parent/legal guardian?
Is a male or female greater than or equal to 18 years old?
If patient has brain metastases, is it asymptomatic and does not require steroids or antiepileptic mediations?
Has Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky > 60%)?

Has adequate bone marrow, renal, and hepatic function:

Absolute neutrophil count (ANC) greater than or equal to 1,500/m^3?
Hemoglobin greater than or equal to 10.0g/dl?
Platelets greater than or equal to 100,000/m^3?
Has adequate renal function defined as serum creatinine < upper limit of normal (ULN) or calculated creatinine clearance > 60 mL/min?
Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) less than or equal to 2.5 times ULN?
Total bilirubin less than or equal to 1.5 times ULN (in patients with evidence of Gilberts disease, elevated bilirubin should not be related to tumor or other liver diseases and should be less than or equal 2 times upper limit of normal)?
Has negative human immunodeficiency virus (HIV) test?
If female, has negative pregnancy test?
Both male and female patients are willing to consent to using effective contraception (hormonal, barrier method or abstinence) prior to study entry, while on treatment and at least 3 months thereafter?

Phase 1 only:

Has recurrent or advanced cancer for whom standard therapy offers no curative potential and also for patients for whom the carboplatin/paclitaxel regimen is considered standard of care?
Has received no more than one previous chemotherapy regimen?
Has evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria?

Phase 2 only:

Has histological or cytological evidence of non small cell lung cancer?
Has evidence of metastatic disease or stage IIIB non small cell lung cancer (NSCL) with pleural effusion is required?

Has no prior chemotherapy for advanced lung cancer?

Note: Patients who received adjuvant or neo-adjuvant chemotherapy more than 12 months prior will be eligible?

Has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan?

EXCLUSION CRITERIA:

Response should be NO

Has any of the following within 6 months prior to study enrollment: myocardial infarction, unstable angina pectoris or uncontrolled angina pectoris, uncontrolled hypertension that is not controllable with antihypertensives, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, clinically significant peripheral vascular disease (Grade II or greater).
Has history of stroke or transient ischemic attack within 6 months?
Has history of pulmonary embolism, deep venous thrombosis or other thrombo-embolic event within 6 months?
Has psychiatric or neurologic illness that would limit compliance with study requirements?
Has severe active infection within 14 days requiring use of intravenous antibiotics before beginning treatment?
Has received any other investigational agents within 30 days of the start of treatment?

Has history of an active malignancy unless curatively treated and risk of recurrence of < 5% at five years, with the exception of:

Adequately treated in situ carcinoma of the cervix
Non-melanomatous skin cancers (basal or squamous cell)?
Has history of severe hypersensitivity reaction to compounds of similar chemical or biologic composition to carboplatin, paclitaxel, or medicines of similar composition to YM155?
Has history of a major surgical procedure, open biopsy, or a significant traumatic injury within 14 days prior to commencing treatment, or the anticipation of the need for a major surgical procedure during the course of the study?
Has other serious illness, medical condition or significant laboratory abnormality that may cause undue risk for the subject's safety, inhibit protocol participation, or interference with interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study?
Phase 2 only: Has mixed tumor of any histology including small cell lung cancer?