A Phase I Trial Of Gemcitabine, 17-Allylaminogeldanamycin (17-AAG) And Cisplatin In Advanced Solid Tumor Patients
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
IV. To define the dose-limiting toxicity of 17-AAG when used in combination with Gemzar and
V. To assess the effect of 17-AAG on surrogate markers when used in combination with Gemzar
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
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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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
United States: Food and Drug Administration
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