17-N-Allylamino-17-Demethoxygeldanamycin and Paclitaxel in Treating Patients With Metastatic or Unresectable Solid Tumor

Study Overview
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Brief Summary
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This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin when given together with paclitaxel in treating patients with metastatic or unresectable solid tumor. Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining 17-N-allylamino-17-demethoxygeldanamycin with paclitaxel may kill more tumor cells

Detailed Description
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OBJECTIVES: I. Determine the maximum tolerated dose and recommended phase II dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) when administered with paclitaxel in patients with metastatic or unresectable solid malignancy. II. Determine the dose-limiting and non-dose-limiting toxic effects of this regimen in these patients. III. Determine the pharmacokinetics of this regimen in these patients. IV. Determine tumor response in patients treated with this regimen. OUTLINE: This is a multicenter, dose-escalation study of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG). Patients receive 17-AAG IV over 1 hour on days 1*, 4, 8, 11, 15 and 18 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. NOTE: *17-AAG is not administered on day 1 of course 1. Cohorts of 3-6 patients receive escalating doses of 17-AAG 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. Once the MTD is determined, 6-12 patients are treated at the recommended phase II dose.

Official Title
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Phase I Study of 17- Allylamino-17 Demethoxygeldanamycin (17-AAG) in Combination With Paclitaxel in Advanced Solid Malignancies

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: tanespimycin
* Drug: paclitaxel
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed solid malignancy Metastatic or unresectable disease Not amenable to standard curative or palliative therapy No known brain metastases Performance status - ECOG 0-2 More than 12 weeks Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 WBC ≥ 3,000/mm^3 AST and ALT ≤ 2.5 times upper limit of normal Bilirubin normal Creatinine normal Creatinine clearance ≥ 60 mL/min QTc < 450 msec for male patients (470 msec for female patients) LVEF > 40% by MUGA No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row) No myocardial infarction within the past year No New York Heart Association class III or IV congestive heart failure No poorly controlled angina No history of uncontrolled dysrhythmia or requirement for antiarrhythmic drugs No history of congenital long QT syndrome No active ischemic heart disease within the past year No left bundle branch block No other significant cardiac disease Not pregnant or nursing Negative pregnancy test Fertile patients must use effective double barrier contraception for at least 1 week before, during, and for at least 2 weeks after study participation No prior allergy to eggs No prior allergic reaction to compounds of similar chemical or biologic composition to 17-AAG or paclitaxel No peripheral neuropathy > grade 1 No concurrent uncontrolled illness No active or ongoing infection No psychiatric illness or social situation that would preclude study compliance No concurrent granulocyte colony-stimulating factors Prior paclitaxel allowed More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered No prior 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) More than 4 weeks since prior radiotherapy No prior radiotherapy that included the heart in the field (e.g., mantle radiotherapy) No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent therapeutic-dose warfarin for anticoagulation No concurrent medications that may prolong QTc interval No other concurrent investigational agents 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (tanespimycin, paclitaxel)<br>Patients receive 17-AAG IV over 1 hour on days 1*, 4, 8, 11, 15 and 18 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. | Drug: tanespimycin<br>* Given IV<br>* Other names: 17-AAG;Drug: paclitaxel<br>* Given IV<br>* Other names: Taxol;Other: laboratory biomarker analysis<br>* Correlative studies<br>Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2 recommended doses of tanespimycin | Tabulated according to the NCI CTC. | 28 days |