Phase I Study of SNX-5422 Mesylate in Adults With Refractory Solid Tumor Malignancies and Lymphomas
- Inhibitors of the chaperone protein Hsp90 are of current interest because of the
central role that Hsp90 plays in the maturation and maintenance of numerous proteins,
such as Her2, critical for tumor cell viability and growth.
- Disruption of Hsp90 function has been shown to cause degradation of multiple Hsp90
client proteins, leading to inhibition of several key signaling pathways. This in turn
results in inhibition of cellular proliferation.
- Determine the maximum tolerated dose (MTD) of SNX-5422 when administered twice a week
for 28 days.
- Characterize the safety profile of SNX-5422 when administered twice a week for 28 days.
- Investigate the effects of SNX-5422 on Hsp90 client proteins using pharmacodynamic (PD)
- Investigate the effects of SNX-5422 on tumor and lymphoma response using the National
Cancer Institute (NCI) Response Evaluation Criteria in Solid Tumors (RECIST) criteria)
and standardized lymphoma criteria, respectively.
- Determine the pharmacokinetic (PK) profile of SNX-2112 and its prodrug SNX-5422 in
- Patients with histologically documented solid tumors and lymphoid malignancies
(lymphoma and CLL) whose disease has progressed following standard therapy, or who have
no acceptable standard treatment options.
- Patients with no major surgery, radiation, or chemotherapy within 4 weeks prior to
study enrollment, and who have recovered from toxicities from prior therapies to at
least eligibility levels.
This will be a Phase I dose escalation study to determine the MTD and recommended Phase II
dose of SNX-5422. SNX-5422 will be administered orally twice a week for 28 days in
continuous cycles until disease progression occurs or the patient meets off-study criteria.
Three to six patients will be enrolled at each dose level, and up to 6 additional patients
at the MTD, for a minimum of up to 36 patients and a maximum of 60 patients.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine the maximum tolerated dose (MTD) of SNX-5422 when administered twice a week for 28 days.
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|