Unspecified Adult Solid Tumor, Protocol Specific
Conditions
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.
Interventions
DRUGtanespimycin
Given IV
DRUGpaclitaxel
Given IV
OTHERlaboratory biomarker analysis
Correlative studies
OTHERpharmacological study
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 recommended doses of tanespimycin | 28 days | Tabulated according to the NCI CTC. |
Countries
United States
Outcome results
None listed