Phase I Trial of PS-341 in Advanced Cancers
OBJECTIVES: I. Determine the dose-limiting toxicity and maximum tolerated dose of PS-341 in
patients with advanced solid tumors or lymphoma. II. Evaluate the pharmacodynamics of this
drug by measuring 20S proteasome inhibition in these patients. III. Assess changes in P53 or
P27, and possibly E2F-1 and cyclin E, in patients with lymphoma in response to this drug.
IV. Evaluate objective tumor response to this drug in these patients. V. Evaluate the
relationship between toxicity and 20S proteasome inhibition in blood and in accessible tumor
tissue in these patients. VI. Evaluate response to treatment with this drug in patients with
measurable or evaluable disease.
OUTLINE: This is a dose-escalation, multicenter study. Patients receive PS-341 IV on days 1
and 4. Treatment repeats every 14 days for at least 2 courses in the absence of unacceptable
toxicity or disease progression. Patients with stable or responding disease may receive
additional courses at the discretion of the treating physician. Cohorts of 3-6 patients
receive escalating doses of PS-341 until the maximum tolerated dose (MTD) is determined. The
MTD is defined as the dose at which 2 of 3 or 6 patients experience dose-limiting toxicity.
Patients are followed at 4 weeks.
PROJECTED ACCRUAL: A maximum of 27 patients will be accrued for this study.
Primary Purpose: Treatment
Franco M. Muggia, MD
New York University School of Medicine
United States: Federal Government
|Beth Israel Deaconess Medical Center||Boston, Massachusetts 02215|
|Massachusetts General Hospital Cancer Center||Boston, Massachusetts 02114|
|NYU School of Medicine's Kaplan Comprehensive Cancer Center||New York, New York 10016|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Brigham and Women's Hospital||Boston, Massachusetts 02115|