Geldanamycin Analogue in Treating Patients With Advanced Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: This phase I trial is studying the side effects and best dose of a geldanamycin analogue in treating patients with advanced cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose for a geldanamycin analogue, 17-allylamino-17-demethoxygeldanamycin (AAG), in patients with advanced malignancies. Determine the toxic effects and dose-limiting toxicity of AAG in this patient population. Determine the safe dose of AAG for a Phase II study. Measure the pharmacokinetic and pharmacodynamic profiles of AAG in these patients. Assess time to tumor progression and any antitumor activity in patients treated with AAG. OUTLINE: This is a dose-escalation study. Patients receive a geldanamycin analogue, 17-allylamino-17-demethoxygeldanamycin (AAG), IV over 15-30 minutes every week. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Patients are followed at 4 weeks. PROJECTED ACCRUAL: Approximately 20-40 patients will be accrued for this study.

Official Title
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A Phase I Pharmacokinetic and Pharmacodynamic Study of 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) (NSC 330507) Via Intravenous Administration in Patients With Advanced Malignancies

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: tanespimycin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically proven malignancies refractory to conventional treatment or for which no standard therapy exists Primary brain tumor or brain metastases allowed if stable symptoms within 2 weeks prior to study and able to give informed consent PATIENT CHARACTERISTICS: Age: 18 to 75 Performance status: WHO 0-2 Life expectancy: At least 3 months Hematopoietic: WBC at least 3,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10.0 g/dL Absolute neutrophil count at least 1,500/mm^3 Hepatic: Bilirubin less than 1.0 mg/dL AST and ALT no greater than 2.5 times upper limit of normal if due to liver metastases No chronic liver disease Renal: Creatinine less than 1.47 mg/dL OR Creatinine clearance greater than 60 mL/min Cardiovascular: No myocardial infarction within the past 6 months No angina requiring treatment within the past 6 months No uncompensated coronary artery disease by electrocardiogram or physical examination No prior transient ischemic attacks, stroke, or peripheral vascular disease LVEF at least 45% Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 4 weeks after study No allergy to egg products No nonmalignant systemic disease that would increase risk No active uncontrolled infection No diabetes mellitus with evidence of severe peripheral vascular disease or diabetic ulcers PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior immunotherapy and recovered Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered No other concurrent chemotherapy Endocrine therapy: At least 4 weeks since other prior endocrine therapy and recovered Concurrent corticosteroids for symptom control allowed if no change in dose requirement within 2 weeks prior to study Radiotherapy: At least 4 weeks since prior radiotherapy (except for palliative reasons) and recovered Concurrent radiotherapy allowed for control of bone pain or as indicated Surgery: Not specified Other: No other concurrent investigational treatment No concurrent treatment with drugs interfering with hepatic CYP3A4 metabolism (e.g., grapefruit juice or warfarin)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: tanespimycin|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-allylamino-17-demethoxygeldanamycin (17-AAG) at 4 weeks |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heat shock protein 90 (HSP90) client protein and co-chaperone changes during first course of treatment |  |  | 
| Pharmacokinetic profile of 17-AAG 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