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
Condition: Head and Neck Cancer; Liver Cancer; Breast Cancer; Gastric Cancer; Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Stomach Neoplasms; Head and Neck Neoplasms; Liver Neoplasms
Intervention: CUDC-101; CUDC-101
Intervention description: CUDC-101 administered as a 1 hour intravenous infusion at the maximum tolerated dose of 275 mg/m2 consecutively for 5 days on each 14 day cycle.; CUDC-101 administered as a 1 hour intravenous infusion at the maximum tolerated dose of 275 mg/m2 on Monday, Wednesday, Friday for three consecutive weeks of each 28 day cycle.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Head and Neck Cancer; Liver Cancer; Breast Cancer; Gastric Cancer; Non-Small Cell Lung Cancer; EGFR; HDAC; Her2; CUDC-101

Summary:

      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.
    

Eligibility criteria:

        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.