Study of Oral Darinaparsin in Patients With Advanced Solid Tumors

Phase I Study of Oral Darinaparsin in Advanced Solid Tumors

This study is a Phase I, dose escalation study of oral darinaparsin for the treatment of advanced solid tumors. Eligible patients could have received any amount of previous therapy.

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.