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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Head and Neck Cancer, Liver Cancer, Breast Cancer, Gastric Cancer, Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: CUDC-101
* Drug: CUDC-101


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: 5 days/week schedule<br> | Drug: CUDC-101<br>* 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.<br>|
| Experimental: Arm B: 3 days/week schedule<br> | Drug: CUDC-101<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Safety and tolerability will be assessed in the two treatment arms and the incidence of adverse events will be compared. | 12-15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Her2, Head and Neck Cancer, Liver Cancer, Breast Cancer, Gastric Cancer, Non-Small Cell Lung Cancer, EGFR, HDAC, CUDC-101