A Phase I and Pharmacologic Study of 17-(Allylamino)-17-Demethoxygeldanamycin (AAG, NSC 330507) in Adult Patients With Solid Tumors
19 Years
N/A
Both
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Non-Hodgkin 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
Trial Information
A Phase I and Pharmacologic Study of 17-(Allylamino)-17-Demethoxygeldanamycin (AAG, NSC 330507) in Adult Patients With Solid Tumors
PRIMARY OBJECTIVES:
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.
Inclusion Criteria
Criteria:
- Platelet count at least 100,000/mm^3
- No leukemia
- No active CNS involvement with tumor
- ECOG 0-2
- Life expectancy: at least 3 months
- Absolute neutrophil count at least 2,000/mm^3
- No New York Heart Association class III or IV heart failure
- No history of myocardial infarction within the past year
- Bilirubin =< upper limit of normal (ULN)
- AST no greater than 2 times ULN (no greater than 98 U/L)
- No uncontrolled dysrhythmias
- No poorly controlled angina
- No serious ventricular arrhythmia (i.e., ventricular tachycardia (VT) or ventricular
fibrillation (VF) >= 3 beats in a row)
- QTc interval =< 450 msec for men or =< 470 msec for women
- LVEF >= 40% by MUGA
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No other serious medical condition that would preclude study participation
- No serious hypersensitivity to egg products
- No concurrent anticancer immunotherapy
- At least 4 weeks since prior chemotherapy and recovered
- No other concurrent anticancer chemotherapy (e.g., cyclophosphamide, doxorubicin,
vincristine, and prednisone [CHOP] or mechlorethamine, vincristine, procarbazine, and
prednisone [MOPP])
- No concurrent anticancer hormonal therapy
- Concurrent glucocorticoids as antiemetics for nonmalignant disease allowed
- At least 4 weeks since prior radiotherapy and recovered
- No concurrent radiotherapy
- No concurrent major surgery
- No concurrent anticancer glucocorticoids
- Creatinine =< ULN or Creatinine clearance at least 60 mL/min
- No concurrent medications that cause QTc prolongation
- Histologically confirmed advanced solid tumor for which no curative therapy exists
- Non-Hodgkin's lymphoma allowed
- No concurrent drugs that interfere with hepatic CYP3A4 metabolism (e.g., grapefruit
juice, ketoconazole, fluconazole, itraconazole, cyclosporine, erythromycin,
clarithromycin, cimetidine, terfenadine, astemizole, indinavir, or nelfinavir
mesylate)
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose of tanespimycin
Outcome Description:
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.
Outcome Time Frame:
28 days
Safety Issue:
No
Principal Investigator
Jean Grem
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Nebraska
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00819
NCT ID:
NCT00019708
Start Date:
June 1999
Completion Date:
Related Keywords:
- Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
- Nodal Marginal Zone B-cell Lymphoma
- Non-Hodgkin 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
- Burkitt Lymphoma
- Leukemia, Lymphocytic, Chronic, B-Cell
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, Large B-Cell, Diffuse
- Lymphoma, Non-Hodgkin
- Lymphoma, B-Cell
- Lymphoma, Large-Cell, Immunoblastic
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Lymphoma, B-Cell, Marginal Zone
- Neoplasms
- Lymphoma, Mantle-Cell
Name | Location |
|---|---|
| University of Nebraska Medical Center | Omaha, Nebraska 68198-3330 |
