Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of CUDC-427 When Given to Patients With Advanced and Refractory Solid Tumors or Lymphoma
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|ClinicalTrials.gov Identifier: NCT01908413|
Recruitment Status : Terminated
First Posted : July 25, 2013
Last Update Posted : December 1, 2016
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma||Drug: CUDC-427||Phase 1|
This is a Phase I, open-label, multicenter, dose-escalation study to evaluate the safety and tolerability of CUDC-427 as a single agent administered orally, in subjects with advanced and refractory solid tumors or lymphoma.
Sequential dose escalation cohorts of oral CUDC-427 are planned. Subject enrollment and dose escalation will proceed according to a standard 3+3 design. In the absence of intolerable toxicity, each subject will receive a minimum of 1 cycle (21 days) of study treatment, and may continue to receive additional cycles until disease progression has been documented or other treatment discontinuation criteria have been met.
No intrasubject dose escalation will be allowed. During the dose escalation phase, up to 3 additional subjects may be enrolled at previously cleared dose levels to better define the safety, tolerability and activity of the study treatment. Similarly, an MTD expansion cohort of up to 12 evaluable subjects may also be enrolled.
Safety and tolerability will be assessed by the incidence and severity of adverse events as assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE v4.03). A Safety Review Committee comprised of the Medical Monitor, Principal Investigators, and Sponsor representatives, will be convened to review safety information and to decide upon dose escalation and further subject enrollment.
The antitumor activity of study treatment will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), or the Revised Response Criteria for Malignant Lymphoma as appropriate for each subject's tumor type.
Exploratory biological markers of CUDC-427 activity will be assessed in tumor samples (where available), peripheral blood mononuclear cells (PBMC) and plasma.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||23 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Oral CUDC-427, an Antagonist of Inhibitors of Apoptosis (IAP) Proteins, When Administered in Subjects With Advanced and Refractory Solid Tumors or Lymphoma|
|Study Start Date :||July 2013|
|Actual Primary Completion Date :||March 2015|
|Actual Study Completion Date :||November 2015|
CUDC-427 as an oral formulation administered daily on a 14 days on/7 days off schedule
- To determine the maximum tolerated dose (MTD) and recommended Phase 2 (monotherapy) dose of oral CUDC-427 administered on a 14 days on/7 days off dosing schedule in subjects with advanced and refractory solid tumors or lymphoma [ Time Frame: 21 days (1 cycle of study treatment) ]
- To assess safety and tolerability [ Time Frame: 21 days ]Number of participants with adverse events assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE, v4.0).
- To assess pharmacokinetics (PK) [ Time Frame: The first day of study drug dosing through the sixteenth day of study drug dosing ]PK parameters to be determined will include apparent oral clearance (Cl/F), apparent volume of distribution (Vd/F), maximum concentration (Cmax), time of maximum concentration (Tmax), half-life (t1/2), area under the curve (AUC), and other relevant parameters.
- To evaluate exploratory biological markers of CUDC-427 activity [ Time Frame: The first day of study drug dosing through the fifteenth day of study drug dosing ]Exploratory biomarkers that may predict or correlate with CUDC-427 biological activity will be assessed in tumor samples, PBMCs and plasma, such as gene signature profile, cellular inhibitor of apoptosis (cIAP) levels, Ki-67 activity, caspase activity, cytokine levels, and other downstream events of IAP inhibition.
- To assess preliminary anti-cancer activity [ Time Frame: 3-12 weeks ]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 RECIST v1.1 for Solid Tumors).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01908413
|United States, Tennessee|
|Sarah Cannon Research Institute|
|Nashville, Tennessee, United States, 37203|
|United States, Texas|
|Southern Texas Accelerated Research Therapeutics|
|San Antonio, Texas, United States, 78229|