A Open-Label, Multiple Ascending Dose Study of DS-3078a, an Oral TORC1/2 Kinase Inhibitor, in Subjects With Advanced Solid Tumors or Lymphomas
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1, Open-Label, Multiple Ascending Dose Study of DS-3078a, an Oral TORC1/2 Kinase Inhibitor, in Subjects With Advanced Solid Tumors or Lymphomas|
- Maximum tolerated dose [ Time Frame: 3 years ]To determine the maximum tolerated dose (MTD) and tentative recommended Phase 2 dose (RP2D) of DS 3078a
- determine the Cmax profile of DS 3078a [ Time Frame: 3 years ]determine the Cmax (maximum concentration) of DS-3078a administered under fed and unfed conditions
- effect on glucose metabolism [ Time Frame: 3 years ]determine the effect of DS-3078a on glucose metabolism by measuring serum glucose and C peptide
- assess pharmacodynamic effects tumor glucose uptake [ Time Frame: 3 years ]assess the pharmacodynamic effects of DS 3078a by determining tumor glucose uptake using (18F) fluorodeoxyglucose positron emission tomography (FDG-PET)
- assess tumor response [ Time Frame: 3 years ]assess tumor response to DS-3078a in subjects with advanced non-Hodgkin lymphomas or advanced solid tumor types in which the mammalian target of rapamycin (mTOR) signaling pathway is frequently activated
- assess pharmacodynamic effects v-akt murine thymoma viral oncogene [ Time Frame: 3 years ]assess the pharmacodynamic effects of DS 3078a by measuring v-akt murine thymoma viral oncogene homolog 1 (Akt) phosphorylation in platelet rich plasma (PRP)
- determine the AUC of DS 3078a [ Time Frame: 3 years ]determine the Area under the concentration versus time curve (AUC) of DS-3078a administered under fed and unfed conditions
- determine the Tmax of DS 3078a [ Time Frame: 3 years ]determine the time of maximum concentyration (Tmax) of DS-3078a administered under fed and unfed conditions
- determine the terminal half-life of DS 3078a [ Time Frame: 3 years ]determine the terminal half-life (T1/2) of DS-3078a administered under fed and unfed conditions
|Study Start Date:||April 2012|
|Study Completion Date:||June 2014|
|Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
Part 1 - Dose escalation of DS-3078a to determine the maximum tolerated dose (MTD) will be guided by the modified continuous reassessment method (mCRM) using a Bayesian logistic regression model (BLRM) following escalation with overdose control (EWOC) principle.
Before starting mCRM, initial dose escalation will proceed following an accelerated titration in which single subjects will be enrolled into sequential dose levels with a dose increment of up to 100% from the previous dose.
Upon completion of Part 1 with established MTD and tentative recommended phase 2 dose (RP2D), the Dose Expansion (Part 2) will begin with the intention of further assessing the safety and tolerability of DS-3078a, confirming the RP2D, determining the Pharmacodynamic response in tumor samples, and evaluating preliminary efficacy of DS-3078a in subjects.
DS-3078a will be administered as oral capsules once daily and will be supplied in 5, 20, 50, and 150 mg capsules.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01588678
|United States, Texas|
|South Texas Accelerated Research Therapeutics|
|San Antonio, Texas, United States, 78229|