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Gemcitabine and Tanespimycin in Treating Patients With Stage IV Pancreatic Cancer
The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by National Cancer Institute (NCI).   Recruitment status was  Active, not recruiting

First Received on December 19, 2007.   Last Updated on January 20, 2011   History of Changes
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: Allocation: Randomized
Primary Purpose: Treatment
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:


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
Experimental: 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. 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
Experimental: 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. 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
Experimental: 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), 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, Florida
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
United States, Minnesota
Minnesota Oncology Hematology, PA - Minneapolis
Minneapolis, Minnesota, United States, 55407
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
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
Investigators
Study Chair: Robert McWilliams, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Charles Erlichman, Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT00577889     History of Changes
Other Study ID Numbers: CDR0000445454, MAYO-MC0542, NCI-7351
Study First Received: December 19, 2007
Last Updated: January 20, 2011
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:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on February 09, 2012