Safety of 24-Hour Infusion of ON 01910.Na in Patients With Advanced Cancer
The primary purpose of this study is to determine the highest dose of ON 01910.Na that can be safely given as an intravenous infusion over 24 hours once a week in a 3-week cycle to patients with advanced solid tumors.
Drug: rigosertib sodium
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Dose Escalation Study of ON 01910.Na by 24 Hour Continuous Infusion Per Week in Patients With Advanced Cancer|
- Number of dose limiting toxicities (DLTs) [ Time Frame: 21 days after first administration of ON 01910.Na ] [ Designated as safety issue: Yes ]
DLTs are defined as:
- Grade 3 non-hematological toxicity other than nausea, vomiting, diarrhea, fever, stomatitis, esophagitis/dysphagia.
- Recurrent grade 3 toxicity uncontrolled by optimal therapy or Grade 4 nausea, vomiting, diarrhea and fever.
- Grade 3 stomatitis and/or esophagitis/dysphagia for > 5 days.
- Grade 4 neutropenia or thrombocytopenia for > 5 days measured at least 2X 2-3 days apart.
- Neutropenic fever, as defined in Protocol.
- Failure to recover neutrophils (> 1,500 per microliter) or platelets (>75,000 per microliter) before the next weekly dose.
- Number of Adverse Events (AEs) [ Time Frame: 30 days after last infusion of study drug ] [ Designated as safety issue: Yes ]All AEs (except Grade 1 and 2 laboratories abnormalities that do not require an intervention) are recorded in Case Report Forms and source documentation.
- Severity of Adverse Events (AEs) [ Time Frame: 30 days after last infusion of study drug ] [ Designated as safety issue: Yes ]Severity of AEs are determined according to Common Terminology Criteria for Adverse Events (Version 3.0)
- Relationship of Adverse Events (AEs) to Study Treatment [ Time Frame: 30 days after last infusion of study drug ] [ Designated as safety issue: Yes ]Relationship assessed as Not related, Unlikely, Possibly, Probably, or, Definitely according to Guidance in Appendix II of Protocol.
- Concentration of ON 01910.Na in plasma versus time [ Time Frame: Up to 48 hours after infusion of study drug during Week 1 in Cycles 1 and 2 ] [ Designated as safety issue: No ]Blood samples will be collected at following time points: Pre-dose; 1 h after start of infusion; 3 h; 6 h; 12 h; 18 h; 24 h; 10 min after end of infusion; 20 min; 30 min; 1 h; 2 h; 4 h; 8 h; 24 h; and, 48 h. Plasma will be prepared from these samples. Concentration of ON 01910.Na will be determined by validated method.
- Change in size of target lesions recorded at baseline [ Time Frame: 30 days after last infusion of study drug ] [ Designated as safety issue: No ]The same method of assessment for each identified and recorded lesion will be used at baseline and each follow-up.
|Study Start Date:||June 2006|
|Study Completion Date:||November 2011|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Drug: rigosertib sodium
- ON 01910.Na Concentrate
- ON 01910.Na
This is an open-label, dose-escalating Phase I study of ON 01910.Na in patients with advanced cancers, who have satisfied the inclusion/exclusion criteria enumerated in this protocol. Patients will receive ON 01910.Na intravenously by 24 hour continuous infusion once every week (3 weeks per cycle), until evidence of disease progression, intolerable adverse events, or withdrawal of patient consent. Safety monitoring will be done for at least 3 weeks before escalation to the next dose level. As of Amendment 7, up to 6 patients with gynecological malignancies will be enrolled at the 2400 mg/m2 dose level to determine the appropriateness of this dose as the Recommended Phase Two Dose (RPTD).
|United States, New York|
|Albert Einstein Cancer Center|
|Bronx, New York, United States, 10461|
|Principal Investigator:||Sridhar Mani, MD||Albert Einstein College of Medicine of Yeshiva University|