The main purpose of this study is to determine the safety and tolerability of orally administered CUDC-101 in cancer patients, and to determine a dose for further testing. This study will also determine how well CUDC-101 is absorbed into the blood after being given orally, assess CUDC-101 blood levels and what happens to the study drug in the body, and study how the body reacts to the study drug and what effects it has on tumors. CUDC-101 has been administered to cancer patients as an intravenous (IV) infusion in other research studies, but has not been studied when given orally.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
200-500 mg CUDC-101, orally administered, twice daily, in continuous 21 day cycles until disease progression or other discontinuation criteria are met.
Karmanos Cancer Institute
Detroit, Michigan, United States
Southern Texas Accelerated Research Therapeutics
San Antonio, Texas, United States
Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose of oral CUDC-101 in subjects with advanced and refractory solid tumors
The highest dose level studied at which fewer than 2 out of 6 subjects (\< 33%) experience a dose limiting toxicity (DLT).
Time frame: 21 days (1 cycle of study treatment)
Assess the bioavailability (BA) of orally administered CUDC-101
Comparison of area under the plasma concentration time curve (AUC) following intravenous and oral administrations.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours post-dose on the first and second day of study drug dosing.
Assess the pharmacokinetics (PK) of orally administered CUDC-101
Pharmacokinetic parameters will include AUC, maximum plasma concentration (Cmax),half-life (T1/2), clearance (Cl) and volume of distribution (Vd).
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours post-dose on the ninth day of study drug dosing
Assess the safety and tolerability of continuous orally administered CUDC-101
Number of participants with adverse events assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE, v4.0).
Time frame: 18 months
Evaluate biomarkers of CUDC-101 activity
Pre- and post-dose changes in acetylated histone H3 protein levels in peripheral blood mononuclear cells (PBMCs), as well as skin and tumor biopsy samples (where available).
Time frame: Day 1 and Day 7 of Cycle 1 dosing.
Assess preliminary anti-cancer activity
Occurrences of complete response, partial response, stable disease and progressive disease as determined by the Response Evaluation Criteria In Solid Tumors (RECIST v1.1).
Time frame: 18 months
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