17-DMAG in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphomas

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

A Phase I Study Of 17-Dimethylaminoethylamino-17-Demethoxygeldanamycin, (17-DMAG) (NSC 707545) In Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00089271
• Other study ID #: NCI-2012-02620
• Secondary ID: PCI-03-153U01CA0
• Status: Completed
• Phase: Phase 1
• First received: August 4, 2004
• Last updated: January 24, 2013
• Start date: July 2004

Study information

• Verified date: January 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

This phase I trial is studying the side effects and best dose of 17-DMAG in treating patients with metastatic or unresectable solid tumors or lymphomas. Drugs used in chemotherapy, such as 17-DMAG, work in different ways to stop cancer cells from dividing so they stop growing or die

Description:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in patients with metastatic or unresectable solid tumors or lymphomas.

II. Determine the safety and toxicity of this drug in these patients. III. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.

IV. Determine the recommended phase II dose of this drug for future studies.

SECONDARY OBJECTIVES:

I. Determine tumor response in patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) IV over 1-6 hours on days 1-3 or 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 1-2 patients receive accelerated escalating doses of 17-DMAG until at least 1 of 2 patients experience dose-limiting toxicity (DLT). Cohorts are then expanded to 3-6 patients who receive escalating doses (in a standard manner) of 17-DMAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT.

Patients are followed at 4 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed solid tumor or lymphoma

• Metastatic or unresectable disease

• Standard curative or palliative measures do not exist or are no longer effective

• No known brain metastases

• Performance status - ECOG 0-2

• Performance status - Karnofsky 60-100%

• More than 12 weeks

• Absolute neutrophil count = 1,500/mm^3

• Platelet count = 100,000/mm^3

• Hemoglobin = 9.0 g/dL

• ALT and AST = 1.5 times upper limit of normal (ULN)

• Bilirubin = normal

• Creatinine = 1.25 times ULN

• Creatinine clearance = 60 mL/min

• QTc < 450 msec for male patients (470 msec for female patients)

• LVEF > 40% by MUGA

• No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation = 3 beats in a row)

• No myocardial infarction or active ischemic heart disease within the past year

• No New York Heart Association class III or IV congestive heart failure

• No poorly controlled angina

• No uncontrolled dysrhythmia requiring medication

• No left bundle branch block

• No history of congenital long QT syndrome

• No other significant cardiac disease

• Pulse oximetry at rest or on exercise > 88%

• No symptomatic pulmonary disease (e.g., chronic obstructive or restrictive pulmonary disease, etc.) or any of the following are allowed:

• Pulmonary disease requiring medication

• History of dyspnea, dyspnea on exertion, or paroxysmal nocturnal dyspnea

• Patients meeting the Medicare criteria for home oxygen or are on oxygen

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective double barrier contraception 1 week before, during, and for at least 2 weeks after study participation

• No uncontrolled illness

• No active or ongoing infection

• No history of allergic reaction attributed to compounds of similar chemical or biological composition to 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG)

• No psychiatric illness or social situation that would preclude study compliance

• No concurrent routine colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

• Concurrent hormonal therapy allowed

• At least 4 weeks since prior radiotherapy and recovered

• No prior radiation that included the heart in the field (e.g., mantle)

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent anticancer agents or therapies

• No concurrent medication that would prolong the QTc interval

• No other concurrent investigational agents

Study Design

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

Related Conditions & MeSH terms

• Anaplastic Large Cell Lymphoma
• Angioimmunoblastic T-cell Lymphoma
• Burkitt Lymphoma
• Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
• Hodgkin Disease
• Intraocular Lymphoma
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, T-Cell
• Leukemia-Lymphoma, Adult T-Cell
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Large-Cell, Anaplastic
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous
• Mycoses
• Mycosis Fungoides
• 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 Hodgkin Lymphoma
• Recurrent Adult T-cell Leukemia/Lymphoma
• Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
• Recurrent Grade 1 Follicular Lymphoma
• Recurrent Grade 2 Follicular Lymphoma
• Recurrent Grade 3 Follicular Lymphoma
• Recurrent Mantle Cell Lymphoma
• Recurrent Marginal Zone Lymphoma
• Recurrent Mycosis Fungoides/Sezary Syndrome
• Recurrent Small Lymphocytic Lymphoma
• Sezary Syndrome
• Splenic Marginal Zone Lymphoma
• Stage III Adult Burkitt Lymphoma
• Stage III Adult Diffuse Large Cell Lymphoma
• Stage III Adult Diffuse Mixed Cell Lymphoma
• Stage III Adult Diffuse Small Cleaved Cell Lymphoma
• Stage III Adult Hodgkin Lymphoma
• Stage III Adult T-cell Leukemia/Lymphoma
• Stage III Cutaneous T-cell Non-Hodgkin Lymphoma
• Stage III Grade 1 Follicular Lymphoma
• Stage III Grade 2 Follicular Lymphoma
• Stage III Grade 3 Follicular Lymphoma
• Stage III Mantle Cell Lymphoma
• Stage III Marginal Zone Lymphoma
• Stage III Mycosis Fungoides/Sezary Syndrome
• Stage III Small Lymphocytic 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 Hodgkin Lymphoma
• Stage IV Adult T-cell Leukemia/Lymphoma
• Stage IV Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary Syndrome
• Stage IV Small Lymphocytic Lymphoma
• Syndrome
• Unspecified Adult Solid Tumor, Protocol Specific
• Waldenstrom Macroglobulinemia
• Waldenström Macroglobulinemia

Intervention

Drug:
• alvespimycin hydrochloride
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

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 alvespimycin hydrochloride		21 days	Yes
Primary	Toxicity graded using the NCI CTCAE version 3.0		Up to 4 weeks	Yes
Primary	Recommended phase II dose (RP2D) of alvespimycin hydrochloride for future studies determined by toxicity assessments		21 days	Yes
Primary	Pharmacokinetics of alvespimycin hydrochloride in blood, urine, and tumor tissue	Analyzed by both non-compartmental and compartmental methods.	21 days	No
Secondary	Tumor response assessed by tumor measurements		Up to 4 weeks	No