Safety of 24-hour Infusion of ON 01910.Na in Combination With Gemcitabine in Advanced Solid Tumors
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Phase I Dose Escalation Study of Gemcitabine and 24 Hour Infusion of ON 01910.Na in Patients With Advanced or Metastatic Solid Tumors|
- Adverse Events and Laboratory Parameters [ Time Frame: Throughout study ]Incidence of adverse signs and/or symptoms (adverse events and laboratory parameters)
- Pharmacokinetics [ Time Frame: MTD confirmation phase of study ]The derived plasma pharmacokinetic parameters of ON 01910.Na administered alone and with gemcitabine at the MTD will also be investigated: Cmax, tmax, terminal half-life, AUC0-last, AUC0-inf., CL, and Vss.
|Study Start Date:||January 2010|
|Study Completion Date:||July 2011|
|Primary Completion Date:||July 2011 (Final data collection date for primary outcome measure)|
Drug: ON 01910.Na
- gemcitabine HCl
- 2´-deoxy-2´,2´-difluorocytidine monohydrochloride (-isomer)
- gemcitabine for injection, USP
- nucleoside metabolic inhibitor
The order of infusion will be gemcitabine first, immediately followed by ON 01910.Na (with the only exception being the first infusion for those patients undergoing PK sampling; where the ON 01910.Na infusion will be given first on this occasion). The dose of gemcitabine will be fixed at 1000 mg/m2 i.v. as a 30 minutes infusion on days 1, 8, and 15 every 28 days. As of Amendment 2, the starting dose of ON 01910.Na is 250 mg/m2 as a 24 hour intravenous (i.v.) infusion on days 1, 8 and 15 of a 28-day course. The dose of ON 01910.Na will be escalated in increments in successive cohorts (dose level (DL) 1 = 250 mg/m2, DL 2 = 650 mg/m2, DL 3 = 1050 mg/m2, DL 4= 1350 mg/m2) of new patients. A course is defined as 4 weeks in length. Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v3.0). A minimum of three new patients will be treated at each dose level with a minimum of a 1 week stagger between the dosing of the first and remaining patients in each new dose cohort. In exceptional circumstances (e.g. where there is one slot available in a cohort and two eligible patients have been screened), the Sponsor may allow four patients to enter a cohort (or seven patients to enter an expanded cohort). A DL -1A (ON 01910.Na = 125 mg/m2) is set in case dose de-escalation is required with the starting dose due to ON 01910.Na-related toxicity. A DL -1A gemcitabine = 750 mg/m2 and DL - 1B at 500 mg/m2 are set in case dose de-escalation is required with the starting and subsequent doses due to gemcitabine-related toxicity. If DLT is not observed in the first three patients, then the dose of ON 01910.Na will be increased to the next level. If DLT occurs in any of the first three new patients in the first course, at least three additional new patients will be treated. If no further DLT is encountered, dose escalation will proceed. Alternately, if DLT is noted in one or more of three additional patients, dose escalation will be terminated and the MTD will be defined as the highest dose level at which none of the first three patients or no more than one of six patients experienced DLT in course 1. All patients receiving doses exceeding the confirmed MTD will have their dose reduced to the MTD; even if apparently tolerating their current dose. Intra-patient dose escalation of ON 01910.Na will be permitted. There will be no limit to the number of courses that could be administered to a patient who is both tolerating and benefiting from therapy.
Escalation to the next dose level will occur only after the third evaluable patient (or sixth, if an expanded cohort), on the previous dose level has been observed for 4 weeks. Dose escalation decisions will be made by a Cohort Review Committee (CRC). Intra-patient dose escalation of ON 01910.Na will be allowed after the third evaluable patient on the next dose level has been observed for 4 weeks with acceptable tolerability.
Once the MTD has been defined, an expanded cohort of 9 to 12 additional patients (depending if 3 or 6 patients were enrolled on the previous cohort) will be enrolled at the MTD dose level in order to further define the safety and tolerability of this regimen, and characterize the pharmacokinetics of ON 01910.Na alone and after gemcitabine, and perform a tumor biomarker study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01165905
|United States, California|
|Department of Medicine, University of California San Francisco|
|San Francisco, California, United States, 94143|
|United States, New York|
|Albert Einstein Cancer Center/Montefiore Medical Center|
|The Bronx, New York, United States, 10461|
|Principal Investigator:||Sridhar Mani, MD||Albert Einstein College of Medicine, Inc.|
|Principal Investigator:||Pamela N. Munster, MD||Department of Medicine, University of California San Francisco|