A Phase I Trial of ZIO-101 in Solid Tumors

Inclusion criteria

• Subjects with histological confirmation solid malignancy refractory to conventional standard therapies for their condition
• Eligible subjects MUST have at least one measurable lesion as defined by RECIST guidelines. If the measurable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology. Measurable lesions MUST not have been in a previously irradiated field or injected with biological agents
• Pediatric subjects will be eligible at the discretion of the primary investigator.
• ECOG performance status score ≤ 2
• Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device), and must have a negative blood or urine pregnancy test within 1 week before beginning treatment. Sexually active men must also use acceptable contraceptive methods
• Subjects must provide written informed consent prior to treatment
• At least 4 weeks from prior completion of prior therapy to day 1 of study drug
• Baseline toxicity assessment ≤ grade 1 except treatment induced alopecia (NCI Common Toxicity Criteria version 3.0)
• Evidence of adequate multi-organ functional status as reflected by the following clinical laboratory values:

• Serum creatinine ≤ 2 times the upper normal limit OR a calculated creatinine clearance ≥ 50 cc/min
• Total bilirubin ≤ 2 times the upper normal limit
• Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal
• Granulocytes in peripheral blood greater than or equal to 1 x 10(9) per liter, hemoglobin greater than or equal to 8.5 g/dL, and platelets greater than or equal to 50,000 /microL

Exclusion criteria

• Uncontrolled systemic infection (documented with microbiological studies)
• Active heart disease as defined by an acute myocardial infarction within the previous 6 months before starting therapy, stable or unstable angina, clinically significant arrhythmia requiring medical management, OR New York Heart Association Classification of Functional Activities. Class 3: Subject has marked limitation in activities due to symptoms, even during less-than-ordinary activity and is comfortable only at rest OR Class 4: Severe limitations. Subject experiences symptoms even while at rest
• Concomitant therapy for solid cancer
• Pregnant subjects and those who are breast-feeding
• History of an invasive second primary malignancy diagnosed within the previous 3 years except for Stage I Endometrial/Cervical Carcinoma or Prostate Carcinoma treated surgically, and non-melanoma skin cancer
• Documented personal or family history of prolonged QT syndrome
• 12 lead electrocardiogram with a corrected QT interval > 460 milliseconds
• History of confusion or dementia
• History of seizure disorder