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

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

A Phase I and Pharmacologic Study of 17-(Allylamino)-17-Demethoxygeldanamycin (AAG, NSC 330507) in Adult Patients With Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00019708
• Other study ID #: NCI-2009-00819
• Secondary ID: NCI-2009-00819UN
• Status: Terminated
• Phase: Phase 1
• First received: July 11, 2001
• Last updated: December 13, 2013
• Start date: June 1999

Study information

• Verified date: December 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00001804

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 45
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

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)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Burkitt Lymphoma
• Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Large-Cell, Immunoblastic
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• 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

Intervention

Drug:
• tanespimycin
Given IV

Locations

Country	Name	City	State
United States	University of Nebraska Medical Center	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of tanespimycin	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.	28 days	No
Secondary	Biomolecular effects of tanespimycin in normal tissues such as peripheral blood and bone marrow mononuclear cells	Changes in the protein expression of the molecular markers will be assessed by western blot analysis.	Up to day 5	No
Secondary	Pharmacokinetics of tanespimycin	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.	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	No