Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Gemcitabine and Tanespimycin in Treating Patients With Stage IV Pancreatic Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Treatment Active 18 and over NCI MAYO-MC0542 MC0542, 7351, NCI-7351, NCT00577889

Objectives

Primary

1. To assess the effect of gemcitabine hydrochloride and tanespimycin (17-AAG) on 6-month survival rate in patients with stage IV pancreatic adenocarcinoma.

Secondary

1. To determine the overall survival of these patients.
2. To determine the time to disease progression (TTP) in these patients.
3. To determine the confirmed response rate and duration of response in these patients.
4. To determine the time to treatment failure in these patients.
5. To determine the adverse events in these patients.

Tertiary

1. 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.
2. To determine the effect of gemcitabine hydrochloride metabolizing enzyme genotype on toxicity, and clinical outcome.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed pancreatic adenocarcinoma
  • Clinical stage IV disease



• No known brain metastases

Prior/Concurrent Therapy:

• 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

Patient Characteristics:

• 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 1 Medicare 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)

 [Note: *Patients who meet the Medicare criteria for home oxygen should be excluded from the study]

Expected Enrollment

Outcomes

6-month survival rate

Overall survival
Time to disease progression
Confirmed response rate
Duration of response
Time to treatment failure
Adverse events
Number of circulating tumor cells
Levels of intracellular targets, such as CDK4, akt, phospho-akt, Hsp90, Hsp70, and CHK1 as measured by immunohistochemistry
Correlation of single nucleotide DNA polymorphisms of tanespimycin (17-AAG) and gemcitabine hydrochloride metabolizing and target genes with survival, progression, response, and adverse events
Correlation of Vav1 expression in primary tumor and circulating tumor cells with clinical outcomes

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 IV over 30 minutes on days 1 and 8 and tanespimycin (17-AAG) 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 17-AAG 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 17-AAG 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 17-AAG 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.

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Robert McWilliams, MD, Protocol chair		Ph: 507-284-2511

U.S.A.
California
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
Michigan
	Detroit
	Barbara Ann Karmanos Cancer Institute
		Clinical Trials Office - Barbara Ann Karmanos Cancer Institute	Ph:  313-576-9363
Minnesota
	Minneapolis
	Minnesota Oncology Hematology, PA - Minneapolis
		Patrick Flynn, MD	Ph:  612-863-8585
	Rochester
	Mayo Clinic Cancer Center
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
Missouri
	Saint Louis
	Center for Cancer Care and Research
		John Eckardt, MD	Ph:  314-628-1210
			Email: jeckardt@tcccr.com
Wisconsin
	Madison
	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
		Clinical Trials Office - University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Ph:  608-262-5223
Hong Kong
	Shatin, New Territories
	Prince of Wales Hospital
		Anthony Chan, MD	Ph:  852-2632-2144
			Email: anthonytcchan@cuhk.edu.hk

Registry Information
Official Title		A Phase II Trial of 17-N-Allylamino-17-Demethoxygeldanamycin (17-AAG) in Combination with Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma
Trial Start Date		2008-03-20
Trial Completion Date		2008-06-30 (estimated)
Registered in ClinicalTrials.gov		NCT00577889
Date Submitted to PDQ		2007-11-26
Information Last Verified		2008-03-30
NCI Grant/Contract Number		CA15083, CM62205