A Phase II Trial of 17-N-Allylamino-17-Demethoxygeldanamycin (17-AAG) in Combination With Gemcitabine in Patients With Metastatic Pancreatic Adenocarcinoma
18 Years
N/A
Both
Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage IV Pancreatic Cancer
Trial Information
A Phase II Trial of 17-N-Allylamino-17-Demethoxygeldanamycin (17-AAG) in Combination With Gemcitabine in Patients With Metastatic Pancreatic Adenocarcinoma
PRIMARY OBJECTIVES:
I. To assess the effect of gemcitabine hydrochloride and tanespimycin (17-AAG) on 6-month
survival rate in patients with stage IV pancreatic adenocarcinoma.
SECONDARY OBJECTIVES:
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.
TERTIARY OBJECTIVES:
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.
Inclusion Criteria:
- Histologically or cytologically confirmed pancreatic adenocarcinoma
- Clinical stage IV disease
- No known brain metastases
- ECOG performance status 0-2
- Life expectancy ≥ 12 weeks
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Total bilirubin normal
- AST ≤ 2.5 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 2 times ULN (5 times ULN if liver metastases are present)
- Creatinine normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Ejection fraction > 40% by echocardiogram
- Patients who received prior anthracyclines must have a normal ejection fraction
by echocardiogram
- QTc < 500 msec
- Pulse oximetry > 88% on room air at rest and after gentle exercise (according to
Group 1Medicare Guidelines)
- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to tanespimycin (17-AAG) or gemcitabine hydrochloride
- No known allergy to eggs
- No concurrent uncontrolled illness including, but not limited to, any of the
following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness/social situations that would limit compliance with study
requirements
- No active ischemic heart disease within the past 12 months
- No history of uncontrolled dysrhythmias
- No congenital long QT syndrome
- No left bundle branch block
- No other significant cardiac disease, including any of the following:
- New York Heart Association class III or IV heart failure
- Myocardial infarction within the past year
- Poorly controlled angina
- Uncontrolled dysrhythmias
- History of serious ventricular arrhythmia (ventricular tachycardia or
ventricular fibrillation ≥ 3 beats in a row)
- No clinically significant interstitial lung disease
- No symptomatic pulmonary disease requiring medication, including any of the
following:
- Dyspnea
- Dyspnea on exertion
- Paroxysmal nocturnal dyspnea
- Significant pulmonary disease requiring oxygen*, including chronic
obstructive/restrictive pulmonary disease
- No pulmonary or cardiac symptoms ≥ grade 2
- No history of cardiac or pulmonary toxicity after receiving anthracyclines (e.g.,
doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride,
bleomycin, or vincristine)
- No prior chemotherapy for metastatic disease
- No prior radiotherapy to the chest
- No prior radiotherapy that potentially included the heart in the field (e.g.,mantle
radiotherapy)
- More than 3 months since prior adjuvant chemotherapy or chemotherapy for locally
advanced disease
- More than 3 weeks since prior radiotherapy
- No concurrent medications that prolong or may prolong QTc
- No concurrent antiarrhythmic drugs
- No concurrent prophylactic colony-stimulating factors
- No other concurrent investigational agents
- No other concurrent anticancer therapy
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Survival rate in patients with metastatic pancreatic adenocarcinoma receiving tanespimycin in combination with gemcitabine hydrochloride
Outcome Description:
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.
Outcome Time Frame:
6 months
Safety Issue:
No
Principal Investigator
Robert McWilliams
Investigator Role:
Principal Investigator
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00156
NCT ID:
NCT00577889
Start Date:
March 2008
Completion Date:
Related Keywords:
- Adenocarcinoma of the Pancreas
- Recurrent Pancreatic Cancer
- Stage IV Pancreatic Cancer
- Adenocarcinoma
- Adenocarcinoma, Mucinous
- Pancreatic Neoplasms
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
