17-N-Allylamino-17-Demethoxygeldanamycin and Paclitaxel in Treating Patients With Metastatic or Unresectable Solid Tumor
- Conditions
- Unspecified Adult Solid Tumor, Protocol Specific
- Interventions
- Registration Number
- NCT00087217
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
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Histologically confirmed solid malignancy
- Metastatic or unresectable disease
-
Not amenable to standard curative or palliative therapy
-
No known brain metastases
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Performance status - ECOG 0-2
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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
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QTc < 450 msec for male patients (470 msec for female patients)
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LVEF > 40% by MUGA
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No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
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No myocardial infarction within the past year
-
No New York Heart Association class III or IV congestive heart failure
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No poorly controlled angina
-
No history of uncontrolled dysrhythmia or requirement for antiarrhythmic drugs
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No history of congenital long QT syndrome
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No active ischemic heart disease within the past year
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No left bundle branch block
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No other significant cardiac disease
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Not pregnant or nursing
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Negative pregnancy test
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Fertile patients must use effective double barrier contraception for at least 1 week before, during, and for at least 2 weeks after study participation
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No prior allergy to eggs
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No prior allergic reaction to compounds of similar chemical or biologic composition to 17-AAG or paclitaxel
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No peripheral neuropathy > grade 1
-
No concurrent uncontrolled illness
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No active or ongoing infection
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No psychiatric illness or social situation that would preclude study compliance
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No concurrent granulocyte colony-stimulating factors
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Prior paclitaxel allowed
-
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
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No prior 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)
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More than 4 weeks since prior radiotherapy
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No prior radiotherapy that included the heart in the field (e.g., mantle radiotherapy)
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No concurrent combination antiretroviral therapy for HIV-positive patients
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No concurrent therapeutic-dose warfarin for anticoagulation
-
No concurrent medications that may prolong QTc interval
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No other concurrent investigational agents
-
No other concurrent anticancer agents or therapies
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (tanespimycin, paclitaxel) tanespimycin 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. Treatment (tanespimycin, paclitaxel) laboratory biomarker analysis 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. Treatment (tanespimycin, paclitaxel) pharmacological study 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. Treatment (tanespimycin, paclitaxel) paclitaxel 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.
- Primary Outcome Measures
Name Time Method Phase 2 recommended doses of tanespimycin 28 days Tabulated according to the NCI CTC.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
University of Pennsylvania Medical Center
🇺🇸Philadelphia, Pennsylvania, United States