SNX-5422 to Treat Solid Tumor Cancers and Lymphomas

Lymphoma Clinical Trial

Official title: Phase I Study of SNX-5422 Mesylate in Adults With Refractory Solid Tumor Malignancies and Lymphomas

Status Completed

Clinical Trial Summary

Background:

SNX-5422 is an experimental drug that inhibits a protein called Hsp90, which is important for the growth of tumor cells.

SNX-5422 has shown some activity against tumors in the laboratory and animal studies.

Objectives:

To determine the highest safe dose, or maximum tolerated dose (MTD), of SNX-5422 that can safely be given to patients with solid tumor cancers and lymphomas when taken twice a week.

To learn how the body's blood and tissue cells react to SNX-5422.

To examine the effects of SNX-5422 on tumors and lymphomas.

Eligibility:

Patients 18 years of age or older who have solid tumor cancers or lymphomas that do not respond to standard therapy or for whom no acceptable standard treatment is available.

Design:

SNX-5422 is taken by mouth twice a week in 28-day cycles. Treatment may continue as long as the cancer does not worsen and side effects are acceptable. Three to six patients are enrolled in the study at a time. Each group is given a higher dose of SNX-5422 than the previous, as long as the preceding dose was tolerated and until the MTD is determined. When the MTD is found, six more patients are enrolled at that dose level.

During the treatment period, patients undergo the following tests and procedures:

• Clinic visits for a physical examination each treatment cycle to check on health status.

• Blood tests for routine laboratory values, to determine how the body handles SNX-5422, and to examine the effects of SNX-5422 on blood cells and other targets.

• Urine tests as needed, depending on the results of blood tests.

• CT scans, or other imaging tests every 8 weeks to evaluate the tumor response to treatment.

• Tumor biopsy (surgical removal of a tissue sample for examination under a microscope) before the first dose of SNX-5422 and again 24 hours after the first dose to see how the drug affects the tumor. This test is optional.

Clinical Trial Description

Background:

• 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.

Objectives:

• 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) assays.

• 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 humans.

Eligibility:

• 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.

Design:

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. ;

Related Conditions & MeSH terms

• Lymphoma
• Neoplasms

• NCT number: NCT00644072
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: March 7, 2008
• Completion date: June 16, 2011