Phase IB Study of Indibulin Using Positron-Emission Tomography (PET) Scans

Inclusion criteria

• Histological or cytological confirmation of advanced cancer, refractory to standard therapies.
• Received at least one prior therapy and requires additional treatment.
• ≥18 years of age.
• ECOG performance score ≤ 2 (see Appendix 3).
• At least one measurable lesion as defined by RECIST (Response evaluation criteria in solid tumors) guidelines (see Appendix 4). 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.
• PET scan showing a standardized uptake value (SUV) of ≥5.0 in at least 1 lesion on an 18F-FDG (fluorine-18-labeled deoxyglucose) scale.
• Life expectancy ≥12 weeks.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements, to be conducted <2 weeks prior to Day 1:

• Creatinine ≤1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≥50 cc/minute
• Total bilirubin ≤1.5 × ULN
• Alanine transaminase (ALT) and aspartate transaminase (AST) ≤2.5 × ULN
• White blood cell count ≥3.0 × 109/L
• Absolute neutrophil count (ANC) ≥1.5 × 109/L
• Platelets ≥100 × 109/L
• Hemoglobin ≥10 g/dL
• Ability to tolerate repeated blood sampling and adequate vascular access.
• Serum glucose levels ≤200 mg/dL.
• Provide written informed consent in compliance with ZIOPHARM policies and the Independent Ethics Committee with jurisdiction over the site.
• Subjects of childbearing potential must agree to use a barrier method of contraception throughout the study and for 3 months after study drug administration.

Exclusion criteria

• New York Heart Association (NYHA) functional class ≥3 or myocardial infarction within 6 months (see Appendix 5).
• Uncontrolled diabetes mellitus
• Uncontrolled cardiac arrhythmia other than asymptomatic atrial fibrillation.
• Pregnancy and/or lactation.
• Uncontrolled systemic infection (documented with microbiological studies)
• Any other anti-cancer or immunological therapy during the study or within 4 weeks of study entry. Mitomycin C or nitrosureas should not be given within 6 weeks of study entry.
• Radiotherapy during the study or within 3 weeks of study entry.
• Surgery within 4 weeks of start of study drug excluding tumor biopsy for pharmacodynamic parameters.
• Investigational drug therapy outside of this trial during or within 4 weeks of study entry.
• 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.
• Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results
• Any condition that is unstable or could jeopardize the safety of the subject and his/her compliance with the study protocol.