17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in Treating Patients With an Advanced Solid Tumor or Lymphoma

March 14, 2012 updated by: National Institutes of Health Clinical Center (CC)

A Phase I Study Of 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17DMAG) With Evaluation Of Hsp90 Client Proteins In Subjects With Solid Tumors And Lymphomas

RATIONALE: Drugs used in chemotherapy, such as 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), work in different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of 17-DMAG in treating patients with an advanced solid tumor or lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in patients with an advanced malignant solid tumor or lymphoma.
  • Determine the dose-limiting toxic effects and toxicity profile of this drug in these patients.

Secondary

  • Compare the effects of this drug on heat shock protein 90 (Hsp90) client proteins when assayed in peripheral blood mononuclear cells (PBMC) vs tumor tissue from patients treated with this drug.
  • Correlate disturbances in key signaling pathways with administration of this drug in these patients.
  • Determine the dose that alters key proteins in the majority of patients treated with this drug.
  • Correlate serum proteomic patterns with target interactions or DMAG clinical effects in patients treated with this drug.
  • Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a single-center, dose-escalation study.

Patients receive 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) IV over 1-2 hour on days 1 and 4 or days 2 and 5 weekly for 4 weeks. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 patients receive escalating doses of 17-DMAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of up to 6 patients experience dose-limiting toxicity. Once the MTD is determined, 10 additional patients are treated at the MTD.

PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study within 2 years.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed malignant solid tumor OR lymphoma

    • Metastatic or unresectable disease
  • Standard curative or palliative measures are not available OR are associated with minimal survival benefit

  • No known brain metastases

    • Treated brain metastases allowed provided they have been stable ≥ 6 months without steroids or anti-seizure medications

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy

  • More than 3 months

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • WBC ≥ 3,000/mm^3
  • Hemoglobin > 8 g/dL

Hepatic

  • AST and ALT ≤ 2 times upper limit of normal
  • Bilirubin ≤ 1.5 times normal
  • PT and PTT ≤ 1.5 times normal (unless due to the presence of lupus anticoagulant or stable anticoagulation)

Renal

  • Creatinine normal OR
  • Creatinine clearance ≥ 60 mL/min

Cardiovascular

  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No orthostatic hypotension > grade 2 (requiring more than brief fluid replacement or other therapy OR with physiological consequences)
  • No New York Heart Association class III or IV heart failure
  • LVEF ≥ 40% by MUGA
  • QTc ≤ 450 msec (470 msec for women)
  • No congenital long QT syndrome
  • No myocardial infarction within the past year
  • No active ischemic heart disease within the past year
  • No history of uncontrolled dysrhythmias
  • No history of serious ventricular arrhythmia (ventricular fibrillation or ventricular tachycardia > 3 premature ventricular contractions in a row)
  • Not requiring antiarrhythmic drugs
  • No poorly controlled angina
  • No left bundle branch block

Pulmonary

  • No uncontrolled symptomatic pulmonary disease, including any of the following:

    • Dyspnea off or on exertion
    • Paroxysmal nocturnal dyspnea
    • Severe chronic obstructive/restrictive pulmonary disease requiring daily chronic medications and oxygen
  • Must not meet the Medicare criteria for home oxygen
  • No sufficiently compromised pulmonary status as measured by baseline pulmonary function tests and DLCO

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 2 months after study participation
  • No known HIV positivity
  • No hyponatremia indicated by sodium < 130 mmol/L
  • No known immunodeficiency syndromes
  • No history of allergic reaction attributed to compounds of similar chemical or biological composition to 17-dimethylaminoethylamino-17-demethoxygeldanamycin (geldanamycin or 17-AAG)
  • No concurrent uncontrolled illness
  • No active or ongoing uncontrolled infection
  • No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • More than 4 weeks since prior biologic therapy and recovered
  • No concurrent prophylactic growth factors

Chemotherapy

  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin, 8 weeks for UCN-01) and recovered

Endocrine therapy

  • See Disease Characteristics
  • Concurrent hormonal therapy for prostate cancer allowed provided patient has metastatic disease that has progressed despite prior hormonal therapy

Radiotherapy

  • More than 4 weeks since prior radiotherapy and recovered
  • No prior radiotherapy that included the heart in the field (e.g., mantle radiotherapy)

Surgery

  • At least 4 weeks since prior major surgery

Other

  • At least 2 weeks since prior participation in a phase 0 study
  • Concurrent bisphosphonates for any cancer allowed
  • Concurrent preventative doses of aspirin or non-steroidal anti-inflammatory drugs allowed
  • No concurrent drugs that may prolong QTc interval
  • No concurrent full anticoagulation on a regular basis
  • No concurrent prophylactic antiemetics
  • No other concurrent investigational agents or therapies
  • No other concurrent anticancer agents or therapies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institutes of Health Clinical Center (CC)

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2004

Primary Completion (Actual)

March 1, 2010

Study Completion (Actual)

December 1, 2010

Study Registration Dates

First Submitted

August 4, 2004

First Submitted That Met QC Criteria

August 4, 2004

First Posted (Estimate)

August 5, 2004

Study Record Updates

Last Update Posted (Estimate)

March 15, 2012

Last Update Submitted That Met QC Criteria

March 14, 2012

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 040218
  • 04-C-0218
  • NCI-6544
  • CDR0000377488

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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