Safety and Tolerability of DS-7423 in Subjects With Advanced Solid Malignant Tumors
This will be a Phase 1, open-label study of DS-7423 to assess its safety and tolerability, identify a RP2D, (recommended Phase 2 Dose) and assess its Pharmacokinetics (PK) (what your body does to process the drugs and how your body gets them out of your system.) and pharmacodynamics (PDy) (Pharmacodynamics is a study of what a drug does to your body) properties in subjects with advanced solid malignant tumors. This study will include 2 parts: part 1-Dose Escalation and part 2-Dose Expansion.
Study Hypothesis: DS-7423 will be safe and tolerable, and will exhibit acceptable PK and PDy properties in subjects with advanced solid malignant tumors for whom standard therapy has failed or for whom no standard therapy exists.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1, Open-Label, Multiple-Escalating-Dose Study of DS-7423, an Orally Administered Dual PI3K/mTOR Inhibitor, in Subjects With Advanced Solid Tumors|
- Adverse Events [ Time Frame: 30 days after last dose ] [ Designated as safety issue: Yes ]All adverse events will be graded according to the NCI-CTCAE, version 4.0
- Plasma pharmacokinetics of DS-7423 [ Time Frame: Cycle 1 - days 1, 2, 8, and 15; Cycle 2 - day 1; end of study ] [ Designated as safety issue: No ]The various pharmacokinetic parameters will be calculated from plasma concentrations of DS-7423 using non-compartmental analyses.
- Effects of DS-7423 on glucose metabolism [ Time Frame: Cycle 1 Days 1, 2, and 15; and end-of-study ] [ Designated as safety issue: No ]The effects of DS-7423 on glucose metabolism will be determined by measuring glucose and C-peptide levels
- Pharmacodynamic effects of DS-7423 in surrogate tissues [ Time Frame: Cycle 1 Days 1, 2, and 15 ] [ Designated as safety issue: No ]The pharmacodynamic effects of DS-7423 will be determined by measuring phosphorylation of Akt in platelet-rich plasma
- Pharmacodynamic effects of DS-7423 in tumors [ Time Frame: Baseline and Cycle 1 Day 4 ] [ Designated as safety issue: No ]The pharmacodynamic effects of DS-7423 will be determined by measuring tumor glucose uptake using (18F) fluorodeoxyglucose-positron emission tomography
- Part 2 - Objective response rate in subjects with advanced colorectal and endometrial cancer [ Time Frame: Baseline and every 2 cycles of treatment for the first 8 cycles and then every 3 cycles thereafter until study drug discontinuation ] [ Designated as safety issue: No ]Objective response rate = the sum of complete response [CR] and partial response [PR] rates as measured using Response Evaluation Criteria in Solid Tumors (RECIST) criteria Version 1.1
- Part 2 - Pharmacodynamic effects of DS-7423 in tumors [ Time Frame: Baseline and Cycle 1 Day 15 ] [ Designated as safety issue: No ]The pharmacodynamic effects of DS-7423 in tumors will be determined by measuring Akt, ribosomal protein S6 (S6), and proline-rich Akt substrate, 40 kDA (PRAS40) phosphorylation in pre- and posttreatment tumor biopsies
|Study Start Date:||July 2011|
|Study Completion Date:||November 2013|
|Primary Completion Date:||November 2013 (Final data collection date for primary outcome measure)|
oral capsule 1mg, 8mg, 48mg, and 80mg strengths administered once daily
Part 1 : Dose-escalation of DS-7423 to determine maximum tolerated dose (MTD) in subjects with advanced solid tumors Part 2 : Dose Expansion: The purpose of Part 2 of this clinical research study is to confirm the safety and tolerability of the MTD of DS-7423 identified in Part 1, and measure the effects of DS-7423 on your cancer. Part 2 will be conducted in subjects with advanced colorectal or endometrial cancer.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01364844
|United States, Michigan|
|Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Tennessee|
|Sarah Cannon Research Institute|
|Nashville, Tennessee, United States, 37203|