A Dose-Finding Study of E7050 Administered Orally to Patients With Advanced Solid Tumors

Inclusion criteria

• Age 18 years.
• Histologically and/or cytologically confirmed metastatic solid tumors, that have progressed after treatment with approved therapies, or for which there are no standard effective therapies available.
• Adequate bone marrow function.
• Adequate renal function.
• Adequate liver function.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Life expectancy > 3 months.
• Be willing and able to comply with the study protocol, and can give written informed consent.

Additional inclusion criterion for the additional 15 patients recruited to the expanded MTD cohort only:

• At least one tumor lesion with diameter >= 2 cm measurable according to Modified RECIST.

Exclusion criteria

• Any condition that may preclude oral intake or oral absorption, history of gastrointestinal malabsorption, or surgery involving gastro- and/or intestinal- anastomosis within 4 weeks prior to starting study drug.
• Untreated or unstable known primary or metastatic central nervous system (CNS) tumors (stability shown by contrast-enhanced computed tomography or magnetic resonance imaging scans at least 8 weeks apart, with the most recent scan obtained within 28 days prior to starting study treatment).
• Known human immunodeficiency virus (HIV), hepatitis B or C, or severe/uncontrolled infection or intercurrent illness (unrelated to tumor).
• Prior surgery, radiotherapy, chemotherapy, biologic therapy or investigational drugs within 4 weeks prior to starting study drug. Prior immunotherapy, hormonal, or molecular targeted therapy within 2 weeks prior to starting study treatment (except gonadorelin analogue therapy for prostate cancer is allowed). (All acute toxicities related to prior treatments should have resolved).
• Clinically significant cardiac impairment or unstable ischemic heart disease including a myocardial infarction within 6 months prior to starting study drug.
• Requiring therapeutic anti-coagulant therapy (prophylactic dose of heparin or low molecular weight heparin is allowed).
• Poorly controlled hypertension (defined as a change in hypertensive therapy within 3 months of starting study drug) or hypertension diagnosed at screening (defined as a repeat blood pressure measurement of 160/90 mmHg or higher).
• Pregnancy or lactation. Female patients of childbearing potential must have a negative pregnancy test before inclusion into the study, and must agree to use medically acceptable methods of contraception (e.g. abstinence, or a double-barrier method [e.g. condom + spermicide, condom + diaphragm with spermicide], or IUD, or have a vasectomised partner) starting at Screening and throughout the entire study period and for 2 months after the last dose of study drug. Those female patients using hormonal contraceptives must also be using an additional approved method of contraception (as described previously) starting at Cycle 1 Day 1, and continuing throughout the entire study period and for 2 months after the last dose of study drug.

Perimenopausal women must have been amenorrheic for at least 12 months; otherwise a pregnancy test is required.

Male patients must agree to use contraceptive methods (e.g., abstinence, or a double-barrier method [e.g., condom + spermicide, condom + partner diaphragm with spermicide]).

Additional exclusion criterion for the additional 15 patients recruited to the expanded MTD cohort only:

• History of any malignancy other than the present malignancy (except treated non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for a minimum of 5 years.