This phase I trial studies the side effects, best way to give, and best doses of tanespimycin with or without gemcitabine hydrochloride and cisplatin in treating patients with advanced solid tumors. Drugs used in chemotherapy, such as tanespimycin, gemcitabine hydrochloride, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Using more than one drug (combination chemotherapy) may kill more tumor cells.
PRIMARY OBJECTIVES: I. To determine the maximally tolerated dose (MTD) of 17-AAG (tanespimycin) when given on days 1 and 8 of every 3 weeks cycle in combination with Gemzar (gemcitabine hydrochloride) and CDDP (cisplatin) (cohorts A, B, and E). II. To determine the MTD of 17-AAG plus Gemzar when Gemzar is given on days 1 and 8 and 17-AAG is given on days 2 and 9 every 3 weeks (cohort C). III. To determine the MTD of 17-AAG plus CDDP when given on days 1 and 8 every 3 weeks (cohort D). IV. To define the dose-limiting toxicity of 17-AAG when used in combination with Gemzar and CDDP. V. To assess the effect of 17-AAG on surrogate markers when used in combination with Gemzar and CDDP. VI. To report any responses observed. OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 3 treatment cohorts. Cohort A (closed to accrual as of 3/2/04)\*: Patients receive escalating doses of gemcitabine hydrochloride intravenously (IV) over 30 minutes, tanespimycin IV over 1 hour, and cisplatin IV over 2 hours on days 1 and 8. NOTE: \*The maximum tolerated dose (MTD) of this 3-drug combination has been determined as of 3/2/04. Cohort B (closed to accrual as of 3/2/05): Patients receive gemcitabine hydrochloride\*\* IV over 30 minutes, tanespimycin IV over 1 hour, and cisplatin\*\* IV over 2 hours on days 1 and 8. Cohort C: Patients receive gemcitabine hydrochloride\*\* IV over 30 minutes and tanespimycin IV over 1-2 hours on days 2 and 9. Cohort D: Patients receive cisplatin\*\* IV over 2 hours and tanespimycin IV over 1-2 hours on days 1 and 8. Cohort E: Patients receive gemcitabine hydrochloride\*\*\*, tanespimycin\*\*\*, and cisplatin\*\*\* as in cohort B. In all cohorts, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 3 months. NOTE: \*\*Gemcitabine hydrochloride and cisplatin dosage is constant, while 17-AAG is escalated in cohorts B, C, and D. NOTE: \*\*\*Gemcitabine hydrochloride dosage is constant, 17-AAG is started at a higher dose level than all other cohorts, and cisplatin dosage is escalated in cohort E.
Study Type
INTERVENTIONAL
Mayo Clinic
Rochester, Minnesota, United States
MTD of tanespimycin, gemcitabine hydrochloride, and cisplatin, determined by incidence of dose-limiting toxicity (DLT) graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time frame: 21 days
Adverse events, graded according to NCI CTCAE version 3.0
The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized within each cohort. The grade 3+ adverse events will also be described and summarized in a similar fashion. This will provide an indication of the level of tolerance for this treatment combination within each cohort. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
Time frame: Up to 30 days after completion of study treatment
Number of responses, determined according to modified Response Evaluation Criteria in Solid Tumors (RECIST)
Responses will be summarized (overall and by tumor type) by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease within each cohort.
Time frame: Up to 3 months after completion of study treatment
Heat shock protein (HSP)70 and HSP90 client protein expression
Descriptive statistics and simple scatterplots will form the basis of presentation of these data. The expression levels of these proteins will be summarized at the different time points as well as percent change in their levels compared (overall and within each patient) between the different time points to assess potential drug interaction. Correlations between these laboratory correlate values and other outcome measures like toxicity and response will be carried out in an exploratory manner.
Time frame: Baseline, 6, and 25 hours after start of infusion on days 1 and 8 of course 1 (cohorts B & D); prior to gemcitabine hydrochloride on day 1; pre-dose, 6, and 25 hours post-tanespimycin dose on day 2 (cohort C)
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Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
78
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