Geldanamycin Analogue in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma
Phase I trial to study the effectiveness of geldanamycin analogue in treating patients who have advanced solid tumors or non-Hodgkin's lymphoma. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die.
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Small Lymphocytic Lymphoma
Splenic Marginal Zone Lymphoma
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Immunoblastic Large Cell Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Small Lymphocytic Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I and Pharmacologic Study of 17-(Allylamino)-17-Demethoxygeldanamycin (AAG, NSC 330507) in Adult Patients With Solid Tumors|
- Maximum tolerated dose of tanespimycin [ Time Frame: 28 days ] [ Designated as safety issue: No ]DLT are defined as any greater than or equal to grade 3 non-hematologic toxicity (except for alopecia of any grade, grade 3 nausea or vomiting during less than maximal antiemetic therapy, and grade 3 fever in the absence of neutropenia and infection), any grade 4 hematologic toxicity (except for anemia of any grade), or the inability to resume treatment by day 42 (longer than two week delay) because of drug related toxicity.
- Biomolecular effects of tanespimycin in normal tissues such as peripheral blood and bone marrow mononuclear cells [ Time Frame: Up to day 5 ] [ Designated as safety issue: No ]Changes in the protein expression of the molecular markers will be assessed by western blot analysis.
- Pharmacokinetics of tanespimycin [ Time Frame: Pre-infusion, 20 minutes, 40, 50, 60 (end of infusion), 70, 80, 95 and 110 minutes, and 2.5, 3, 4, 5, 6.5, 8, 10, 14 and 24 hours ] [ Designated as safety issue: No ]Determined by HPLC with photodiode array detection. The pharmacokinetic parameters that will be determined for parent drug include the maximum plasma concentration (Cmax), time of maximum plasma concentration (Tmax), area under the concentration-time curve (AUC), terminal half-life, clearance and volume of distribution.
|Study Start Date:||June 1999|
|Primary Completion Date:||April 2010 (Final data collection date for primary outcome measure)|
Experimental: Treatment (tanespimycin)
Patients will receive infusions of tanespimycin analogue twice a week in weeks 1 and 3.
Other Name: 17-AAG
I. To determine the maximum tolerated dose of geldanamycin analogue (AAG) in patients with advanced solid tumors.
II. To determine the toxic effects of this drug in this patient population. III. To determine the biochemical and molecular effects of this drug in normal and accessible tumor tissue in these patients.
IV. To determine the pharmacokinetics of this drug in these patients. V. To assess any antitumor activity of this drug in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive geldanamycin analogue (AAG) IV over 1-6 hours once daily on days 1, 4, 15, and 18. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 10 patients are treated at the MTD.
Patients are followed every 6 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00019708
|United States, Nebraska|
|University of Nebraska Medical Center|
|Omaha, Nebraska, United States, 68198|
|Principal Investigator:||Jean Grem||University of Nebraska|