This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Tumor growth and metastasis is believed to depend at least in part on the ability of the tumor to induce neovascularization. Therefore angiogenesis inhibitors may play a role either in prevention of tumor growth or in decreasing tumor propensity for metastasis. Thalidomide has been identified as an angiogenesis inhibitor and there is considerable interest in the use of thalidomide and its analogs as anticancer drugs. CC-5013 is a derivative of thalidomide currently under study for the treatment of patients with multiple myeloma, solid tumors including glioma and metastatic melanoma, myelodysplastic syndromes, Crohn's disease, and congestive heart failure. This will be a phase I dose escalation study to determine the maximum tolerated dose (MTD) and recommended phase II dose of CC-5013 in children with refractory solid tumors (excluding brain tumors) and myelodysplastic syndromes (MDS). CC-5013 will be administered daily for 21 days with a 1 week rest. One course therefore will consist of 28 days. The choice of this schedule among the various schedules used in adult studies is based on it apparently lower incidence of myelosuppression, observation of activity in preliminary studies, and the selection of this schedule for pivotal trials by the manufacturer. The starting dose will be 15 mg/m2/day (approximately equivalent to 25 mg/day in an adult) given once daily, rounded to the nearest 5 mg. Dose escalation will proceed in increments of approximately 30%. Patients with MDS will also be eligible; these patients will receive a dose of 5 mg/m2/day in order to further evaluate tolerability, activity, and biologic end-points in this patient population. These patients will not participate in the dose escalation portion of the protocol.
Showing the most recent 10 out of 459 publications
