Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over NCI NCI-04-C-0218 04-C-0218, 6544, NCI-6544, NCT00088868

Special Category: NCI Web site featured trial

Objectives

Primary

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

Secondary

1. 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.
2. Correlate disturbances in key signaling pathways with administration of this drug in these patients.
3. Determine the dose that alters key proteins in the majority of patients treated with this drug.
4. Correlate serum proteomic patterns with target interactions or DMAG clinical effects in patients treated with this drug.
5. Determine the pharmacokinetics of this drug in these patients.

Entry 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

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

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/mm³
• Platelet count ≥ 100,000/mm³
• WBC ≥ 3,000/mm³
• 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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Shivaani Kummar, MD, Principal investigator		Ph: 301-435-5402 Email: kummars@exchange.nih.gov

Related Information

Web site for additional information
Featured trial article

Registry Information
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
Trial Start Date		2004-06-24
Registered in ClinicalTrials.gov		NCT00088868
Date Submitted to PDQ		2004-06-16
Information Last Verified		2007-05-13

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