Phase I Study To Determine The Safety Of Halofuginone In Patients With A Solid Progressive Tumor

OBJECTIVES:

• Determine the toxicity profile, maximum tolerated dose, and dose-limiting toxic effects of halofuginone hydrobromide in patients with progressive advanced solid tumors.
• Establish a recommended dose of this drug for phase II study.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive oral halofuginone hydrobromide once daily on days 1 and 4-14 of course 1 and on days 1-14 of subsequent courses. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-3 patients receive escalating doses of halofuginone hydrobromide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 20% of patients experience acute dose-limiting toxicity. After the MTD is reached, 6-12 additional patients are treated at dose levels preceding the MTD until the recommended dose for phase II study is determined. The recommended dose for phase II study is defined as the dose preceding the MTD that allows a 90% dose intensity for 2 months with no greater than grade 2 toxicity in 80% of the patients.