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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Terminated

CT.gov ID

NCT00019708

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: tanespimycin	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

To determine the maximum tolerated dose of geldanamycin analogue (AAG) in patients with advanced solid tumors.
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.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Jun 1, 1999

Actual Primary Completion Date :

Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (tanespimycin) Patients will receive infusions of tanespimycin analogue twice a week in weeks 1 and 3.	Drug: tanespimycin Given IV Other Names: 17-AAG

Arm

Intervention/Treatment

Experimental: Treatment (tanespimycin)

Patients will receive infusions of tanespimycin analogue twice a week in weeks 1 and 3.

Drug: tanespimycin

Given IV

Other Names:

17-AAG

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of tanespimycin [28 days]
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.

Secondary Outcome Measures

Biomolecular effects of tanespimycin in normal tissues such as peripheral blood and bone marrow mononuclear cells [Up to day 5]
Changes in the protein expression of the molecular markers will be assessed by western blot analysis.
Pharmacokinetics of tanespimycin [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]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)