Clinical trial NCT00006362: PS-341 in Treating Patients With Advanced Cancer
Official title: A Phase I and Pharmacologic Study of the Proteasome Inhibitor PS-341 in Patients With Advanced Solid Tumors and B-cell Lymphoproliferative Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Precancerous Condition
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: 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
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
Study officials:
affiliation: Mayo Clinic
name: Alex A. Adjei, MD, PhD
role: STUDY_CHAIR
References: