17-N-Allylamino-17-Demethoxygeldanamycin and Paclitaxel in Treating Patients With Metastatic or Unresectable Solid Tumor
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
OBJECTIVES:
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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.
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Determine the dose-limiting and non-dose-limiting toxic effects of this regimen in these patients.
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (tanespimycin, 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. |
Drug: tanespimycin
Given IV
Other Names:
Drug: paclitaxel
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Phase 2 recommended doses of tanespimycin [28 days]
Tabulated according to the NCI CTC.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically confirmed solid malignancy
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Metastatic or unresectable disease
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Not amenable to standard curative or palliative therapy
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No known brain metastases
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Performance status - ECOG 0-2
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More than 12 weeks
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Absolute neutrophil count ≥ 1,500/mm^3
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Platelet count ≥ 100,000/mm^3
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WBC ≥ 3,000/mm^3
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AST and ALT ≤ 2.5 times upper limit of normal
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Bilirubin normal
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Creatinine normal
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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
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No New York Heart Association class III or IV congestive heart failure
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No poorly controlled angina
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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
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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
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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
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No concurrent medications that may prolong QTc interval
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No other concurrent investigational agents
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No other concurrent anticancer agents or therapies
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Pennsylvania Medical Center | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Suresh Ramalingam, University of Pennsylvania Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2012-02610
- PCI-03-152
- U01CA099168
- U01CA062502
- CDR0000373824