Gemcitabine and Tanespimycin in Treating Patients With Stage IV Pancreatic Cancer - Full Text View

Sponsor:	Mayo Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00577889

Purpose

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and tanespimycin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying three different schedules of gemcitabine and tanespimycin to see how well they work in treating patients with stage IV pancreatic cancer.

Condition	Intervention	Phase
Pancreatic Cancer	Drug: gemcitabine hydrochloride Drug: tanespimycin	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	A Phase II Trial of 17-N-Allylamino-17-Demethoxygeldanamycin (17-AAG) in Combination With Gemcitabine in Patients With Metastatic Pancreatic Adenocarcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: 17-(Allylamino)-17-demethoxygeldanamycin Gemcitabine Gemcitabine hydrochloride IPI-504

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

6-month survival rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival [ Designated as safety issue: No ]
Time to disease progression [ Designated as safety issue: No ]
Confirmed response rate [ Designated as safety issue: No ]
Duration of response [ Designated as safety issue: No ]
Time to treatment failure [ Designated as safety issue: No ]
Adverse events [ Designated as safety issue: Yes ]
Number of circulating tumor cells [ Designated as safety issue: No ]
Levels of intracellular targets, such as CDK4, akt, phospho-akt, Hsp90, Hsp70, and CHK1 as measured by immunohistochemistry [ Designated as safety issue: No ]
Correlation of single nucleotide DNA polymorphisms of tanespimycin (17-AAG) and gemcitabine hydrochloride metabolizing and target genes with survival, progression, response, and adverse events [ Designated as safety issue: Yes ]
Correlation of Vav1 expression in primary tumor and circulating tumor cells with clinical outcomes [ Designated as safety issue: No ]

Estimated Enrollment:	72
Study Start Date:	March 2008
Estimated Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental 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. Beginning with course two (and for all subsequent courses), 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.	Drug: gemcitabine hydrochloride given IV Drug: tanespimycin given IV
Arm II: Experimental 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. Beginning with course two (and for all subsequent courses), 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.	Drug: gemcitabine hydrochloride given IV Drug: tanespimycin given IV
Arm III: Experimental 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), 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.	Drug: gemcitabine hydrochloride given IV Drug: tanespimycin given IV

Detailed Description:

OBJECTIVES:

Primary

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

Secondary

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

Tertiary

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.
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 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed pancreatic adenocarcinoma
- Clinical stage IV disease
No known brain metastases

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00577889

Locations

United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
Minnesota Oncology Hematology, PA - Minneapolis
Minneapolis, Minnesota, United States, 55407
United States, Missouri
Center for Cancer Care and Research
Saint Louis, Missouri, United States, 63141
United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Hong Kong
Prince of Wales Hospital
Shatin, New Territories, Hong Kong

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:

Robert McWilliams, MD

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Mayo Clinic Cancer Center ( Charles Erlichman )
Study ID Numbers:	CDR0000445454, MAYO-MC0542, NCI-7351
Study First Received:	December 19, 2007
Last Updated:	October 30, 2009
ClinicalTrials.gov Identifier:	NCT00577889 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the pancreas
stage IV pancreatic cancer
recurrent pancreatic cancer

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Pancreatic Neoplasms
Physiological Effects of Drugs
Neoplasms by Site
Therapeutic Uses
Gemcitabine
Endocrine Gland Neoplasms
Digestive System Neoplasms

Neoplasms by Histologic Type
Endocrine System Diseases
Enzyme Inhibitors
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Carcinoma
Neoplasms
Digestive System Diseases
Radiation-Sensitizing Agents
Pancreatic Diseases
Adenocarcinoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on February 08, 2010