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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00088868
First received: August 4, 2004
Last updated: March 14, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Lymphoma
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: alvespimycin hydrochloride
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase I Study Of 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17DMAG) With Evaluation Of Hsp90 Client Proteins In Subjects With Solid Tumors And Lymphomas

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 40
Study Start Date: June 2004
Study Completion Date: December 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00088868

Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Principal Investigator: Shivaani Kummar, MD NCI - Medical Oncology Branch
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00088868     History of Changes
Obsolete Identifiers: NCT00086008
Other Study ID Numbers: 040218, 04-C-0218, NCI-6544, CDR0000377488
Study First Received: August 4, 2004
Last Updated: March 14, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
unspecified adult solid tumor, protocol specific
anaplastic large cell lymphoma
intraocular 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 small lymphocytic 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 immunoblastic large cell lymphoma
stage III adult lymphoblastic 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 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 immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV grade 1 follicular lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Immunoblastic
Duodenal Neoplasms
Ileal Neoplasms
Jejunal Neoplasms
Neoplasms
Intestinal Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Duodenal Diseases
Intestinal Diseases
Ileal Diseases
Jejunal Diseases

ClinicalTrials.gov processed this record on April 16, 2014