Phase I Trial of PS-341 in Advanced Cancers
18 Years
N/A
Both
Lymphoma, Small Intestine Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Franco M. Muggia, MD
Investigator Role:
Study Chair
Investigator Affiliation:
New York University School of Medicine
Authority:
United States: Federal Government
Study ID:
CDR0000067212
NCT ID:
NCT00004002
Start Date:
July 1999
Completion Date:
Related Keywords:
- Lymphoma
- Small Intestine Cancer
- Unspecified Adult Solid Tumor, Protocol Specific
- stage IV adult Hodgkin lymphoma
- recurrent adult Hodgkin lymphoma
- stage IV cutaneous T-cell non-Hodgkin lymphoma
- recurrent cutaneous T-cell non-Hodgkin lymphoma
- small intestine lymphoma
- unspecified adult solid tumor, protocol specific
- 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
- stage IV adult T-cell leukemia/lymphoma
- recurrent adult T-cell leukemia/lymphoma
- primary central nervous system non-Hodgkin lymphoma
- AIDS-related peripheral/systemic lymphoma
- AIDS-related primary CNS lymphoma
- intraocular lymphoma
- stage IV mantle cell lymphoma
- recurrent mantle cell lymphoma
- angioimmunoblastic T-cell lymphoma
- anaplastic large cell lymphoma
- stage IV mycosis fungoides/Sezary syndrome
- recurrent mycosis fungoides/Sezary syndrome
- 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
- Lymphoma
- Lymphoma, Non-Hodgkin
- Lymphoma, Large-Cell, Immunoblastic
- Duodenal Neoplasms
- Ileal Neoplasms
- Jejunal Neoplasms
- Intestinal Neoplasms
Name | Location |
|---|---|
| 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 |
