PS-341 in Treating Patients With Advanced Solid Tumors or Lymphoma

Sponsor

NYU Langone Health (Other)

Overall Status

Completed

CT.gov ID

NCT00004002

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of PS-341 in treating patients who have advanced solid tumors or lymphoma that have not responded to previous treatment.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Small Intestine Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: bortezomib	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

Phase I Trial of PS-341 in Advanced Cancers

Study Start Date :

Jul 1, 1999

Actual Primary Completion Date :

Oct 1, 2001

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS: Histologically confirmed advanced solid tumor or lymphoma that has failed standard therapy and no standard options available No leukemia or myeloma CNS lesions allowed if adequately treated by surgery and/or radiotherapy and symptomatically stable on maintenance glucocorticoids and not requiring anticonvulsants for at least 3 months

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: SGOT no greater than 2.5 times upper limit of normal Bilirubin no greater than 1.5 mg/dL Renal: Creatinine no greater than 1.5 mg/dL Cardiovascular: No acute ischemia or significant conduction abnormality (i.e., bifascicular block or 2nd or 3rd degree AV blocks) Other: No other serious medical or psychiatric illness Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior bone marrow transplantation with high-dose chemotherapy or radiolabeled monoclonal antibody therapy for lymphoma patients Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks since nitrosoureas) Endocrine therapy: See Disease Characteristics Radiotherapy: At least 4 weeks since prior radiotherapy Surgery: At least 2 weeks since prior major surgery Other: See Disease Characteristics No concurrent antiretroviral therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
2	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
4	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
5	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York	United States	10016