A Phase Ib Expansion Study Investigating the Safety, Efficacy, and Pharmacokinetics of Intravenous CUDC-101 in Subjects With Advanced Head and Neck, Gastric, Breast, Liver and Non-small Cell Lung Cancer Tumors

A Phase Ib Open Label, Expansion Study to Investigate the Safety, Efficacy, and Pharmacokinetics of Intravenous CUDC-101 in Subjects With Advanced Head and Neck, Gastric, Breast, Liver and Non-small Cell Lung Cancer Tumors

This is a phase Ib open label, expansion study of CUDC-101 in patients with advanced head and neck, gastric, breast, liver, and non-small cell lung cancer tumors. CUDC-101 is a multi-targeted agent designed to inhibit epidermal growth factor receptor (EGFR), human epidermal growth factor receptor Type 2 (Her2) and histone deacetylase (HDAC). The study is designed to compare the safety and tolerability of CUDC-101 when administered at the maximum tolerated dose on either a 5 days/week schedule or a 3 days/week schedule.

Inclusion Criteria:

• Subjects with histopathologically confirmed diagnosis of advanced breast, gastric, head and neck, liver and non-small cell lung cancer.

  • For subjects with non-small cell lung cancer only:

    • Most recent treatment must be erlotinib and subjects must have had a radiographic partial or complete response to treatment as defined by RECIST criteria and should be currently progressing after the documented response.
    • A documented mutation in EGFR exons 19 or 21

• Subjects must have no further standard of care options or have refused standard therapy

• Measurable or evaluable disease

• Age ≥ 18 years

• ECOG performance < 2

• Life expectancy ≥ 3 months

• If female, neither pregnant or lactating

• If of child bearing potential, must use adequate birth control

• Absolute neutrophil count ≥ 1,500/µL; platelets ≥ 100,000/µL;

• Creatinine ≤ 1.5x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60mL/min/1.73m2

• Total bilirubin ≤ 1.5x ULN; AST/ALT ≤ 2.5x ULN. In subjects with documented liver metastases, the AST/ALT may be ≤ 5x ULN

• Prothrombin time ≤1.5x ULN, unless receiving therapeutic anticoagulation

• Serum magnesium and potassium within normal limits (may use supplements to achieve normal values)

• Subjects with brain metastases are eligible if controlled on a stable dose ≤ 10mg prednisone/day or its equivalent dose of steroids

• Able to render informed consent and to follow protocol requirements.

Exclusion Criteria:

• Anticancer therapy within 4 weeks of study entry.
• Use of investigational agent(s) within 30 days of study entry
• History of cardiac disease with a New York Heart Association (NYHA) Class II or greater congestive heart failure (CHF), myocardial infarction (MI) or unstable angina in the past 6 months prior to Day 1 of treatment, serious arrhythmias requiring medication for treatment.
• Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C. Subjects with liver cancer and hepatitis may be eligible.