A Dose Escalation Study of Hydroxyurea in Combination With SCH900776 in Advanced Malignant Solid Tumors

Summary

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).

Timeline

Start

2012-03

Primary completion

2013-12

Completion

2013-12

Drugs

Indications