A Phase I, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of ABC294640 in Patients With Advanced Solid Tumors
PRIMARY OBJECTIVES:
I. To assess safety and determine the maximum tolerated dose (MTD) and the dose limiting
toxicities (DLT) of ABC294640 (sphingosine kinase-2 inhibitor ABC294640) in patients with
solid organ tumors. (Part I) II. To assess the safety and tolerability of ABC294640 at the
MTD in an expanded cohort of pancreatic cancer patients. (Part II)
SECONDARY OBJECTIVES:
I. To establish the dose of ABC294640 recommended for future phase II protocols. (Part I)
II. To describe the pharmacokinetics of ABC294640 in patients with solid organ tumors. (Part
I) III. To describe the effects of ABC294640 on plasma levels of sphingosine 1-phosphate in
patients with solid organ tumors. (Part I) IV. To assess antitumor activity of ABC294640 in
patients with solid organ tumors by objective radiographic assessment using Response
Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. (Part I) V. To describe the
pharmacokinetics of ABC294640 in pancreatic cancer patients. (Part II) VI. To describe the
effects of ABC294640 on plasma levels of sphingosine 1-phosphate in pancreatic cancer
patients. (Part II) VII. To assess antitumor activity of ABC294640 in pancreatic cancer
patients by objective radiographic assessment using RECIST 1.1 criteria. (Part II)
OUTLINE: This is a dose-escalation study.
Patients receive sphingosine kinase-2 inhibitor ABC294640 orally (PO) twice daily (BID) on
days 1-28. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.
After completion of study treatment, patients are followed up monthly for 1 year.
Interventional
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) defined as highest dose of ABC294640 at which 0 or 1 patient of 6 experiences a DLT.
MTD defined as the highest dose at which 0 or 1 patient of 6 experiences a DLT. The DLT rate will be estimated with its 95% confidence interval.
Patients will be followed until the point in time when no more than 1 of 6 patients has a Dose Limiting Toxicity (DLT) in cycle 1, and expected 54 days.
Yes
Melanie Thomas
Principal Investigator
Medical University of South Carolina
United States: Institutional Review Board
CTO 101504
NCT01488513
August 2011
Name | Location |
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Medical University of South Carolina | Charleston, South Carolina 29425-0721 |