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

Sponsor

National Institutes of Health Clinical Center (CC) (NIH)

Overall Status

Completed

CT.gov ID

NCT00088868

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Lymphoma Small Intestine Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: alvespimycin hydrochloride	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

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

Study Start Date :

Jun 1, 2004

Actual Primary Completion Date :

Mar 1, 2010

Actual Study Completion Date :

Dec 1, 2010

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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