Phase I Study of Oral Darinaparsin in Advanced Solid Tumors

Inclusion Criteria:

- Subjects with histological or cytological confirmation of advanced cancer (solid
tumor) that is refractory to standard therapies for their condition;

- Men and women of ≥18 years of age;

- ECOG performance score ≤2

- Eligible subjects with solid tumors MUST have at least one measurable lesion as
defined by RECIST 1.1 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;

- 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 Baseline:

- Creatinine ≤1.5 × upper limit of normal (ULN) OR a calculated creatinine
clearance ≥50 cc/min

- Total bilirubin ≤2 × ULN

- Alanine transaminase (ALT) and aspartate transaminase (AST)≤3 × ULN

- Granulocytes in peripheral blood ≥1 × 109/L, hemoglobin ≥10 g/dL, and platelets
≥50,000 /µL

- Adequate vascular access for repeated blood sampling;

- Men and women of childbearing potential must agree to use effective contraception
from Screening through the duration of Study participation;

- Written informed consent in compliance with ZIOPHARM policies and the Human
Investigation Review Committee (IEC/IRB) having jurisdiction over the site.

Exclusion Criteria:

- Arsenic allergy.

- New York Heart Association (NYHA) functional class ≥3 myocardial infarction (see
Appendix 3) within 6 months.

- Uncontrolled cardiac arrhythmia other than asymptomatic atrial fibrillation; a QTc
≥450 msec; or a ≥Grade 2 atrioventricular (AV) block or left bundle branch block
(LBBB); or documented history of prolonged QTc.

- Pregnant and/or lactating women.

- Uncontrolled systemic infection (documented with microbiological studies).

- Metastatic brain or meningeal tumors.

- Patients with seizure disorder requiring medication (such as anti-epileptics)

- History of confusion or dementia or neurological condition that could mask a
potential adverse response to the Study Drug, which may include transient ischemic
attack, Parkinson's disease, thrombotic or hemorrhagic stroke, Alzheimer's, and other
neurological disorders.

- Anticancer chemotherapy or immunotherapy during the study or within four weeks of
Study entry (mitomycin C or nitrosureas should not be given within 6 weeks of Study
entry)

- Radiotherapy during study or within 3 weeks of Study entry.

- Major surgery within 4 weeks of start of Study Drug dosing.

- Other Investigational drug therapy during this trial within four weeks prior to Study
entry.

- History of 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 patient's participation in the study or evaluation of Study results.

- Any condition that is unstable or could jeopardize the safety of the patient and
his/her compliance in the Study.