| Exclusion Criteria: | 1) Symptomatic or progressive brain tumors or brain or leptomeningeal (CNS) metastases requiring clinical intervention, except if they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 2 weeks before starting treatment with E7107. A brain scan is not required unless needed to confirm treatment.
2) Any of the following laboratory parameters: a) hemoglobin < 9 g/dL (5.6 mM) b) neutrophils < 1.5 x 10^9/L c) platelets < 100 x 10^9/L d) serum bilirubin > 25 micromol/L (1.5 mg/dL) e) liver function tests (defined as AST and ALT) with values > 3 x ULN (5 x ULN if liver metastases are present) f) serum creatinine > 1.5 x ULN or creatinine clearance < 40 mL/min
3) Positive history of HIV, active hepatitis B or active hepatitis C or severe/uncontrolled inter-current illness or infection
4) Clinically significant cardiac impairment or unstable ischemic heart disease (greater than Class II according to NYHA classification) including a myocardial infarction within six months of study start
5) Bleeding or thrombotic disorders, or using therapeutic dosages of anticoagulants
6) History of alcoholism, drug addiction, or any psychiatric or psychological condition which, in the opinion of the Investigator, would impair study compliance
7) Women who are pregnant or breast-feeding. Women of childbearing potential with either a positive serum pregnancy test at screening, a positive urine pregnancy test at the beginning of any cycle, or no pregnancy test. Women of childbearing potential unless using two forms of contraception, one of which must be a barrier method. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
8) Fertile men and fertile women who are not willing to use contraception, or fertile men or fertile women with a partner who is not willing to use contraception
9) Patients with a marked screening or baseline prolongation of QT/QTc interval using the Fridericia formula (ie, repeated demonstration of a QTc interval > 450 msec); a history of additional risk factors for TdP (eg, heart failure, hypokalaemia, history of Long QT Syndrome).
10) Patients who have had radiation to >/= 25% of their bone marrow (eg, pelvic radiation)
11) Patients who have a history of previous Grade 2 or higher hypersensitivity to pladienolide B or derivatives and excipients of the formulation
12) Patients with significant comorbid disease or condition, which in the Investigator's opinion would exclude the patient from the study
13) Patients who have received an organ allograft ie, requiring immunosuppressive therapy
14) Beginning 2 weeks prior to dosing, patients are not allowed to take drugs that are strong CYP3A4 inhibitors (including grapefruit juice and herbal supplements) or inducers (including herbal supplements). Use of CYP-metabolized drugs that have a narrow therapeutic window, or are strong inhibitors or inducers of other CYPs should be discussed with the Sponsor and used with caution (see Section 10.9, Prior and Concomitant Therapy and Appendix 9 for a list of these medications).
15) After MTD has been reached: Second malignancy within the past 5 years, except for carcinoma in situ of the cervix, basal cell carcinoma of the skin. |