A Dose Escalation Study of Hydroxyurea in Combination With SCH900776 in Advanced Malignant Solid Tumors
This is an open label Phase I study with two parts. Part Two with SCH900776 in combination with hydroxyurea will not be pursued at this time.
Part One investigates monotherapy with oral hydroxyurea. The primary objective is to determine whether a tolerated dose (TD) of hydroxyurea as a single agent can increase the percentage of tumor cells in S and G2 phase of the cell cycle. For this reason, all patients in Part One must have a tumor lesion accessible for a skin punch biopsy. Tumor biopsies will be obtained on two separate occasions: prior to hydroxyurea and at 16-18h after starting hydroxurea therapy on day 1 only.
A baseline 12-lead ECG will be obtained from each study participant. Single-agent hydroxyurea will be administered on days 1, 8 and 15 of a 28 day cycle, for ONE cycle only. On these days oral hydroxyurea will be started in the late afternoon and administered every 4 hours for a total of 6 doses.
Venous (up to 10 mL) blood samples will be obtained at time zero (pretreatment), 30 min, 1h, 1.5 2, 2.5, 3.0, 3.5 and 4h following the first oral dose of hydroxyurea, and pretreatment and at the same times following the sixth oral dose of hydroxyurea (i.e., 20, 20.5, 21, 21.5, 22, 22.5, 23, 23.5 and 24 h).
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I Dose Escalation Study of Hydroxyurea in Combination With SCH900776 in Advanced Malignant Solid Tumors|
- Percentage of tumor cells in S and G2 phase of the cell cycle [ Time Frame: 16 hours post dose. ]A tissue biopsy is collected at 16 hours post dose.
- Blood concentrations of single agent hydroxyurea at multiple timepoints. [ Time Frame: Blood samples are collected within 24 hours of initial hydoroxyurea dose. ]Pharmacokinetic-pharmacodynamic modeling of drug concentrations/exposure to tumor molecular pharmacodynamics will be done using appropriate Emax or sigmoid Emax direct PK-PD models. Blood samples: time 0 (pretreatment), 30 min, 1h, 1.5 2, 2.5, 3.0, 3.5 and 4h following the first oral dose of hydroxyurea, and pretreatment and at the same times following dose 6 (i.e., 20, 20.5, 21, 21.5, 22, 22.5, 23, 23.5 and 24 h)
|Study Start Date:||March 2012|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01521299
|Principal Investigator:||Margit M McGowan, DO||Dartmouth-Hitchcock Medical Center|