17-Dimethylaminoethylamino-17-Demethoxygeldanamycin (17-DMAG) in Treating Patients With Metastatic Solid Tumors or Tumors That Cannot Be Removed By Surgery

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 the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase I trial is studying the side effects and best dose of 17-DMAG in treating patients with metastatic solid tumors or tumors that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose, dose-limiting toxicity, and recommended phase II dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in patients with unresectable or metastatic solid tumors. Determine the feasibility, safety, and toxicity profile of this drug in these patients. Secondary Determine the clinical pharmacokinetic profile of this drug in these patients. Determine tumor response in patients treated with this drug. Determine the biologically effective dose. OUTLINE: This is an open-label, non-randomized, dose-escalation, multicenter study. Patients receive 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) IV over 1 hour on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 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 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients are treated at the MTD. After completion of study treatment, patients are followed for 28 days. PROJECTED ACCRUAL: Approximately 25-35 patients will be accrued for this study within 12-18 months.

Official Title
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A Cancer Research UK Phase I Trial to Evaluate the Safety, Tolerability and Pharmacokinetics of 17-Dimethylaminoethyl-amino-17-Demethoxygeldanamycin (17-DMAG) Given as a Once Weekly Infusion in Patients With Advanced Solid Tumors

Conditions
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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 or cytologically confirmed solid tumor Unresectable or metastatic disease Standard curative or palliative measures do not exist OR are no longer effective OR patient refused such measures No known brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy More than 12 weeks Hematopoietic Absolute neutrophil count > 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9.0 g/dL Hepatic Bilirubin normal ALT and AST ≤ 1.5 times upper limit of normal No chronic liver disease Hepatitis B or C negative Renal Creatinine normal OR Creatinine clearance normal Cardiovascular No symptomatic New York Heart Association class III-IV cardiac disease No myocardial infarction within the past year No active ischemic heart disease within the past year No poorly controlled angina No uncontrolled dysrhythmia or dysrhythmias requiring antiarrhythmic drugs No transient ischemic attack No stroke No peripheral vascular disease No congenital long QT syndrome No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row) QTc < 450 msec (for men) and 470 msec (for woman) LVEF > 40% by MUGA No left bundle branch block Pulmonary No symptomatic pulmonary disease requiring medication, including any of the following: Dyspnea with or without exertion Paroxysmal nocturnal dyspnea Oxygen requirement Significant pulmonary disease (e.g., chronic obstructive/restrictive pulmonary disease Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception 4 weeks before, during, and for 6 months after completion of study treatment No known HIV positivity No other malignancy within the past 5 years except adequately treated cone biopsied carcinoma in situ of the cervix or basal cell or squamous cell skin cancer No ongoing or active infection No diabetes mellitus (with evidence of severe peripheral vascular disease or ulcers) No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness PRIOR CONCURRENT THERAPY: Biologic therapy More than 4 weeks since prior immunotherapy Concurrent epoetin alfa allowed Chemotherapy More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) No prior 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) Endocrine therapy More than 4 weeks since prior endocrine therapy Concurrent luteinizing hormone-releasing hormone analogues for androgen-insensitive prostate cancer and rising prostate-specific antigen allowed Radiotherapy More than 4 weeks since prior radiotherapy (except for palliative treatment) No prior irradiation field that potentially included the heart (e.g., mantle) Surgery Not specified Other Recovered from all prior therapy Concurrent bisphosphonates allowed At least 5 half-lives since prior and no concurrent medication that prolong QTc No other concurrent anticancer or investigational agents No concurrent grapefruit juice

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
Allocation: Non-Randomized
Masking: None (Open Label)


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 |
| --- | --- | --- |
| Recommended phase II dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) at 28 days after treatment |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heat shock protein 90 (HSP90) client protein and co-chaperone changes up to 29 days after treatment |  |  | 
| Tumor response by RECIST criteria every 6 weeks while on study |  |  | 
| Clinical pharmacokinetic profile established during the first course of treatment |  |  | 

 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