PS-341 in Treating Patients With Advanced Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor 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 cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose and toxicity of PS-341 in patients with advanced malignancies. Determine, in a preliminary manner, the therapeutic activity of this regimen in these patients. OUTLINE: This is a dose-escalation, multicenter study. Regimen A: Patients receive PS-341 IV twice weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. 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 preceding that at which 1 of 3-4 or 2 of 6 patients experience dose-limiting toxicity. Regimen B: Once the MTD has been determined in regimen A, patients receive PS-341 IV twice weekly for 2 weeks. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed for 3 months. PROJECTED ACCRUAL: A maximum of 78 patients will be accrued for this study within 14 months.

Official Title
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A Phase I and Pharmacologic Study of the Proteasome Inhibitor PS-341 in Patients With Advanced Solid Tumors and B-cell Lymphoproliferative Disorders

Conditions
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Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Precancerous Condition, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: bortezomib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven advanced malignancy, including non-Hodgkin's lymphoma (NHL), for which there is no known standard therapy that is potentially curative or definitely capable of extending life expectancy Patients with B-cell lymphoproliferative disorders and a leukemic phase are eligible once the maximum tolerated dose is established NHL patients must meet the following conditions: No greater than 25% of bone marrow involved No symptomatic brain metastases Prior brain metastases allowed if definitively treated (radiotherapy and/or surgery) and stable for at least 8 weeks PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 12 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST or ALT no greater than 2.5 times ULN (5 times ULN if liver involvement) Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No New York Heart Association class III or IV heart disease Other: No uncontrolled infection Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior biologic therapy or immunotherapy No concurrent immunotherapy Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics No prior radiotherapy to greater than 30% of bone marrow At least 4 weeks since prior radiotherapy No concurrent radiotherapy Surgery: See Disease Characteristics Other: No concurrent antiretroviral therapy (HAART) for HIV positive patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: bortezomib|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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monoclonal gammopathy of undetermined significance, isolated plasmacytoma of bone, extramedullary plasmacytoma, refractory multiple myeloma, Waldenstrom macroglobulinemia, stage III multiple myeloma, stage IV chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, unspecified adult solid tumor, protocol specific, B-cell chronic lymphocytic leukemia, untreated hairy cell leukemia, progressive hairy cell leukemia, initial treatment, refractory hairy cell leukemia, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV adult Burkitt lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, primary systemic amyloidosis, stage IV mantle cell lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, stage IV marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma