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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Lymphoma, Small Intestine Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: alvespimycin hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: alvespimycin hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage IV small lymphocytic lymphoma, recurrent mycosis fungoides/Sezary syndrome, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, 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 immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, angioimmunoblastic T-cell lymphoma, small intestine lymphoma, Waldenström macroglobulinemia, recurrent cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent adult T-cell leukemia/lymphoma, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma