About the Phase I Dose Escalation Trial
The Phase I clinical trial is designed as a standard dose escalation study in which a tablet form of CUDC-101 will be orally administered to patients with advanced or refractory solid tumors at two study centers in the United States. The primary objectives are to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose of oral CUDC-101 and to assess the bioavailability and pharmacokinetics of orally administered CUDC-101. The secondary objectives of this study are to assess safety and tolerability, to evaluate biomarkers of CUDC-101 activity and to assess preliminary anti-cancer activity.
The bioavailability of oral CUDC-101 will be assessed among patients enrolled in the first 3 dose level cohorts, who will initially receive single, matched IV and oral doses of CUDC-101 prior to initiating oral twice daily study treatment in the dose escalation portion of the study.
In the absence of dose limiting toxicity, each patient will receive oral CUDC-101 twice daily for a minimum of 21 days of continuous daily dosing (1 cycle), and may continue to receive additional cycles of study treatment until disease progression or other treatment discontinuation criteria are met.About CUDC-101 CUDC-101 is designed as a first-in-class therapeutic to simultaneously inhibit HDAC, EGFR and Her2. To date, Curis has completed a Phase I dose escalation clinical trial of the IV formulation of CUDC-101 in 25 patients with advanced, refractory solid tumors and a Phase I expansion trial in which IV CUDC-101 was administered to 46 patients with specific tumor types, including breast, gastric, head and neck, liver and non-small cell lung cancers. The Phase I expansion trial was designed as an open-label study in which patients were treated with CUDC-101 at the MTD, which was determined in the Phase I dose escalation study to be 275 milligrams per meter squared. The primary objectives of this study were to assess the safety and tolerability of CUDC-101 when administered as a one-hour IV infusion on either a five days per week schedule (one week on/one week off) or a three days per week schedule (three weeks on/one week off).