Dose Escalation Study of Safety and Tolerability of AT-406 in Patients With Advanced Solid Tumors and Lymphomas
The purpose of this study is to determine the safety profile and the maximum dose of Debio 1143 (AT-406) that can be given to humans. This study is also designed to measure how much Debio 1143 (AT-406) gets into the blood stream (pharmacokinetics), and how Debio 1143 (AT-406) interacts with proteins related to cancer that the drug is targeted to affect (pharmacodynamics).
Drug: Debio 1143 (AT-406)
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I, Open Label, Multi-Center, Dose Escalation Study of the Safety, Tolerability, Pharmacodynamic and Pharmacokinetic Properties of Orally Administered AT-406 in Patients With Advanced Solid Tumors and Lymphomas|
- Maximally Tolerated Dose [ Time Frame: 1 cycle, or any time during treatment ] [ Designated as safety issue: Yes ]The primary endpoint of this study is to characterize the safety, and determine the maximum tolerated dose and schedule of Debio 1143 (AT-406) when administered to patients with advanced cancer. Patients will receive Debio 1143 (AT-406) on days 1-5, and 15-19 of a 28 day cycle, days 1-5 of a 21 day cycle, or days 1-14 of a 21 day cycle. For the purpose of determining the MTD, dose limiting toxicities will be evaluated at any time. For the purpose of dose escalation, dose limiting toxicities will be evaluated through the end of 1 cycle.
- Pharmacokinetic [ Time Frame: Days 1-5 of Cycle 1 ] [ Designated as safety issue: Yes ]A secondary endpoint of this study is to determine the pharmacokinetic parameters of Debio 1143 (AT-406) in plasma and urine, and preliminary metabolism profile of Debio 1143 (AT-406).
- Pharmacodynamic [ Time Frame: Cycle 1 ] [ Designated as safety issue: No ]A secondary endpoint of this study, provided that adequate amounts of tissue are available, is to evaluate the interaction of Debio 1143 (AT-406) with IAP family members (e.g., xIAP, cIAP-1, cIAP-2, etc.). Patient participation in this aspect of the study is optional.
- Efficacy [ Time Frame: After a minimum of 2 cycles. ] [ Designated as safety issue: No ]A secondary endpoint to this study is to identify any anti-tumor activity of Debio 1143 (AT-406) that may be observed in the course of the trial. Applicable solid tumor or lymphoma response criteria will be used, accordingly.
- Correlation of Efficacy to Pharmacokinetic and/or Pharmacodynamic Effects of Debio 1143 (AT-406) [ Time Frame: Anytime during Debio 1143 (AT-406) treatment ] [ Designated as safety issue: No ]A secondary endpoint of this study is to correlate pharmacokinetic and pharmacodynamic effects of Debio 1143 (AT-406) with any observed antitumor activity of Debio 1143 (AT-406).
|Study Start Date:||February 2010|
|Estimated Study Completion Date:||September 2014|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Experimental: Debio 1143 (AT-406)
Open label study. All patients participating in the study will receive Debio 1143 (AT-406).
Drug: Debio 1143 (AT-406)
Oral Debio 1143 (AT-406) will be administered in a dose escalation study to determine the maximally tolerated dose in humans. Patients will receive Debio 1143 (AT-406) on days 1-5, and 15-19 of a 28 day cycle, or days 1-5 of a 21 day cycle, repeated until progression or unacceptable toxicity occurs.
Ascenta Therapeutics, Inc. is conducting a clinical trial of the compound Debio 1143 (AT-406), a small molecule second mitochondria-derived activator of caspase C (Smac) mimetic. In vivo and in vitro studies have demonstrated that Debio 1143 (AT-406) induces cell death in several tumor models by inhibiting XIAP (X linked IAP), cIAP-1 (cellular IAP-1) and cIAP-2 (cellular IAP-2), thus releasing initiator and effector caspases to promote apoptosis. This protocol is a Phase I, dose-escalation, open-label, multi-center study conducted in patients with advanced solid tumors and lymphomas to evaluate the safety, tolerability and pharmacology of Debio 1143 (AT-406) in humans when administered orally.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01078649
|United States, Michigan|
|University of Michigan Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Study Director:||Claudio Zanna, MD||Debiopharm SA|