Geldanamycin Analogue in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma

National Cancer Institute (NCI)

Status and phase

Terminated

Phase 1

Conditions

Stage IV Small Lymphocytic Lymphoma

Stage IV Grade 2 Follicular Lymphoma

Stage IV Marginal Zone Lymphoma

Stage IV Adult Diffuse Small Cleaved Cell Lymphoma

Stage IV Adult Diffuse Mixed Cell Lymphoma

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue

Splenic Marginal Zone Lymphoma

Recurrent Adult Diffuse Small Cleaved Cell Lymphoma

Recurrent Grade 3 Follicular Lymphoma

Recurrent Marginal Zone Lymphoma

Non-Hodgkin Lymphoma

Recurrent Adult Diffuse Mixed Cell Lymphoma

Recurrent Grade 1 Follicular Lymphoma

Stage IV Adult Lymphoblastic Lymphoma

Recurrent Adult Immunoblastic Large Cell Lymphoma

Stage IV Grade 3 Follicular Lymphoma

Recurrent Adult Lymphoblastic Lymphoma

Stage IV Adult Diffuse Large Cell Lymphoma

Unspecified Adult Solid Tumor, Protocol Specific

Recurrent Small Lymphocytic Lymphoma

Stage IV Adult Immunoblastic Large Cell Lymphoma

Recurrent Grade 2 Follicular Lymphoma

Recurrent Adult Diffuse Large Cell Lymphoma

Nodal Marginal Zone B-cell Lymphoma

Recurrent Adult Burkitt Lymphoma

Stage IV Adult Burkitt Lymphoma

Stage IV Mantle Cell Lymphoma

Stage IV Grade 1 Follicular Lymphoma

Treatments

Drug: tanespimycin

Study type

Interventional

Funder types

NIH

Identifiers

NCT00019708

UNMC 170-04

T98-0075 (Other Identifier)

CDR0000066965

NCI-2009-00819 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

45 patients

Sex

All

Ages

19+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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)