A Phase II Trial of 17-N-Allylamino-17-Demethoxygeldanamycin (17-AAG) in Combination With Gemcitabine in Patients With Metastatic Pancreatic Adenocarcinoma
I. To assess the effect of gemcitabine hydrochloride and tanespimycin (17-AAG) on 6-month
survival rate in patients with stage IV pancreatic adenocarcinoma.
I. To determine the overall survival of these patients. II. To determine the time to disease
progression (TTP) in these patients. III. To determine the confirmed response rate and
duration of response in these patients.
IV. To determine the time to treatment failure in these patients. V. To determine the
adverse events in these patients.
I. To determine the effects of treatment on molecular targets, such as CDK4, akt,
phospho-akt, Hsp90, Hsp70, and CHK1, and correlate these with clinical endpoints, including
survival at 6 months, TTP, response rate, and overall survival.
II. To determine the effect of gemcitabine hydrochloride metabolizing enzyme genotype on
toxicity, and clinical outcome.
OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance
status (0, 1, or 2). Patients are randomized to 1 of 3 treatment arms.
ARM I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days
1 and 8 and tanespimycin IV over 1 hour on day 9 of course one.
ARM II: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and
tanespimycin IV over 1 hour on days 2 and 9 of course one.
ARM III: Patients receive gemcitabine hydrochloride IV over 30 minutes on day 8 and
tanespimycin IV over 1 hour on days 1 and 9 of course one. Beginning with course two (and
for all subsequent courses), all patients receive gemcitabine hydrochloride IV over 30
minutes on days 1 and 8 and tanespimycin IV over 1 hour on days 2 and 9.
Treatment repeats every 3 weeks in the absence of disease progression or unacceptable
toxicity. Blood samples are collected at baseline and periodically during treatment for
pharmacogenetic studies. Tumor tissue samples that are available are also collected for
laboratory studies. Samples are analyzed for number of circulating tumor cells, levels of
intracellular targets (e.g., CDK4, akt, phospho-akt, Hsp90, Hsp70, and CHK1), single
nucleotide DNA polymorphisms, and Vav1 expression. Samples are analyzed by reverse
transcriptase-polymerase chain reaction, immunofluorescence, and immunohistochemistry.
After completion of study treatment, patients are followed periodically for up to 2 years.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Survival rate in patients with metastatic pancreatic adenocarcinoma receiving tanespimycin in combination with gemcitabine hydrochloride
A patient that is alive at 6 months is considered a treatment "success". The largest success proportion where the proposed treatment regimen would be considered ineffective in this patient population is 40%, and the smallest success proportion that would warrant subsequent studies with the proposed regimen in this patient population is 60%. Estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
United States: Food and Drug Administration
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