Phase I Study in Advanced Solid Tumors

IBL1002:Phase I Study of Indibulin in Advanced Solid Tumors

Dose escalating study of orally administered indibulin at twice daily schedule in subjects with solid tumors.

Inclusion Criteria

1. Subjects with histological or cytological confirmation of advanced cancer, refractory to standard therapies for their condition

2. ≥ 18 years of age

3. ECOG performance score ≤ 2 (see Appendix 3)

4. Eligible subjects MUST have at least one measurable lesion as defined by RECIST 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.

5. Life-expectancy ≥ 12 weeks

6. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted < 2 weeks prior to Baseline:

   • Creatinine ≤ 1.5 X upper limit of normal (ULN) OR a calculated creatinine clearance ≥ 50 cc/min
   • Total bilirubin ≤ 1.5 X ULN
   • Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 X ULN
   • White blood cell count ≥3.0 x 109/L
   • Absolute Neutrophil Count (ANC) ≥1.5 x 109/L
   • Platelets ≥100 x 109/L
   • Hemoglobin ≥ 10 g/dL

7. Written informed consent in compliance with ZIOPHARM policies and the Human Investigation Review Committee with jurisdiction over the site.

Exclusion Criteria

1. New York Heart Association (NYHA) functional class ≥3 or myocardial infarction within 6 months (see Appendix 5)
2. Uncontrolled cardiac arrhythmia other than asymptomatic atrial fibrillation
3. Pregnant and/or lactating female (a reliable method of contraception must be used in all men and in women of childbearing potential during the study and for 3 months after last study drug administration).
4. Uncontrolled systemic infection (documented with microbiological studies)
5. Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry. Mitomycin C or nitrosureas should not be given within 6 weeks of study entry.
6. Radiotherapy during the study or within 3 weeks of study entry
7. Surgery within 4 weeks of start of study drug excluding tumor biopsy for pharmacodynamic parameters
8. Investigational drug therapy outside of this trial during or within 4 weeks of study entry
9. 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
10. Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results
11. Any condition that is unstable or which could jeopardize the safety of the subject and his/her compliance with the study protocol.