Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of CUDC-907 in Patients With Lymphoma or Multiple Myeloma
This is a phase I, open-label, dose-escalation study of CUDC-907 in patients with refractory or relapsed lymphoma or multiple myeloma. CUDC-907 is a multi-targeted agent designed to inhibit phosphoinositide 3-kinase(PI3K)and histone deacetylase (HDAC). The study is designed to assess the safety, including the maximum tolerated dose, the pharmacokinetics, and the anti-cancer activity of CUDC-907.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Open Label, Multi-center, Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Orally Administered CUDC-907, a PI3K and HDAC Inhibitor, in Subjects With Refractory or Relapsed Lymphoma or Multiple Myeloma|
- To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of oral CUDC-907 in patients with relapsed or refractory lymphoma or multiple myeloma [ Time Frame: 21 days (1 cycle of study treatment) ] [ Designated as safety issue: Yes ]The highest dose level studied at which fewer than 2 out of 6 subjects (< 33%) experience a dose limiting toxicity (DLT).
- To assess the safety and tolerability of CUDC-907 [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]Number of participants with adverse events assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE, v4.0).
- To assess pharmacokinetics (PK) of oral CUDC-907 [ Time Frame: Pre-dose to 24 hours post-dose on the first and fifteenth day of study drug dosing ] [ Designated as safety issue: No ]Pharmacokinetic parameters will include area under the concentration-time curve (AUC), maximum plasma concentration (Cmax), half-life (T1/2), clearance (Cl) and volume of distribution (Vd).
- To evaluate biomarkers of CUDC-907 activity [ Time Frame: Day 1, Day 8, and Day 15 of Cycle 1 dosing. ] [ Designated as safety issue: No ]
Pre- and post-dose changes in acetylated histone H3 protein levels in peripheral blood mononuclear cells (PBMCs) on Day 1 and Day 15 of Cycle 1 dosing.
Pre-dose values in acetylated histone H3 protein levels in PBMCs on Day 8 of Cycle 1 dosing.
- To assess preliminary anti-cancer activity of CUDC-907 [ Time Frame: 18 months ] [ Designated as safety issue: No ]The Investigator will evaluate each subject for response to therapy according to standard response criteria for each individual subject's tumor type (e.g., Revised Response Criteria for Malignant Lymphoma and the International Uniform Response Criteria for Multiple Myeloma).
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||April 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
30-180 mg/day CUDC-907, orally administered, once daily, in continuous 21 day cycles until disease progression or other discontinuation criteria are met.
CUDC-907 administered orally, once daily, with meals.
This is a Phase I, open-label, multi-center dose-escalation trial evaluating the safety and tolerability of CUDC-907 as a single agent administered orally, once daily, to patients with relapsed or refractory lymphoma or multiple myeloma.
Sequential dose escalation cohorts of oral CUDC-907 are planned. Subject enrollment and dose escalation will proceed according to a standard 3+3 design. In the absence of DLT, each subject will be treated for a minimum of 21 days of continuous daily dosing, and may continue to receive additional treatment until disease progression has been documented or other treatment discontinuation criteria have been met. No intrasubject dose escalation will be allowed. An MTD expansion cohort of up to 12 evaluable subjects may also be enrolled in order to better define the safety, tolerability and activity of the study treatment.
Safety and tolerability will be assessed by the incidence and severity of adverse events as determined by NCI Common Terminology Criteria for Adverse Events (CTCAE v4.03).
The antitumor activity of study treatment will be assessed according standard response criteria as appropriate for each individual subject's tumor type (e.g., Revised Response Criteria for Malignant Lymphoma and the International Uniform Response Criteria for Multiple Myeloma).
Exploratory biological markers of activity will be assessed in PBMC and plasma.
|United States, New York|
|Memorial Sloan-Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Amy Copeland, RN, MSN, CNS 212-639-6104 email@example.com|
|Principal Investigator: Anas Younes, MD|
|United States, Tennessee|
|Sarah Cannon Research Institute||Recruiting|
|Nashville, Tennessee, United States, 37203|
|Contact: Heather Pedigo 615-329-7432 Heather.Pedigo@scresearch.net|
|Principal Investigator: Jesus Berdeja, MD|
|United States, Texas|
|MD Anderson Cancer Center||Not yet recruiting|
|Houston, Texas, United States, 77030|
|Principal Investigator: Yasuhiro Oki, MD|
|Study Director:||Maurizio Voi, MD||Curis, Inc.|