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Gemcitabine Hydrochloride and Tanespimycin in Treating Patients With Stage IV Pancreatic Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00577889
First received: December 19, 2007
Last updated: July 23, 2014
Last verified: September 2013

December 19, 2007
July 23, 2014
March 2008
January 2011   (final data collection date for primary outcome measure)
Six Month Survival Rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
A patient that is alive at 6 months is considered a treatment "success". 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.
6-month survival rate
Complete list of historical versions of study NCT00577889 on ClinicalTrials.gov Archive Site
  • Overall Survival Time [ Time Frame: Assessed up to 2 years from registration ] [ Designated as safety issue: No ]
    Overall Survival time is defined as the time from registration to death due to any cause. Estimated using the method of Kaplan-Meier.
  • Time to Disease Progression [ Time Frame: Time from registration to documentation of disease progression, assessed up to 2 years ] [ Designated as safety issue: No ]

    The time to disease progression is defined as the time from registration to the time of confirmed disease progression using the Response Evaluation Criteria In Solid Tumors (RECIST). Estimated using the method of Kaplan-Meier.

    Complete Response (CR): Disappearance of all target lesions and normalization of tumor biomarkers (CA 19-9 or CEA).

    Partial Response (PR): At least a 30% decrease in the sum of largest dimension(LD) of target lesions taking as reference the baseline sum LD.

  • Confirmed Response Rate [ Time Frame: 2 consecutive evaluations at least 4 weeks, up to 6 courses of treatment ] [ Designated as safety issue: No ]

    A confirmed response is defined as a complete response (CR) or partial response (PR) observed in two consecutive evaluations at least 4 weeks apart using the Response Evaluation Criteria In Solid Tumors (RECIST). Estimated using the method of Kaplan-Meier.

    Complete Response (CR): Disappearance of all target lesions and normalization of tumor biomarkers (CA 19-9 or CEA).

    Partial Response (PR): At least a 30% decrease in the sum of largest dimension(LD) of target lesions taking as reference the baseline sum LD.Evaluated using RECIST criteria.

  • 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
Not Provided
Not Provided
 
Gemcitabine Hydrochloride and Tanespimycin in Treating Patients With Stage IV Pancreatic Cancer
A Phase II Trial of 17-N-Allylamino-17-Demethoxygeldanamycin (17-AAG) in Combination With Gemcitabine in Patients With Metastatic Pancreatic Adenocarcinoma

This randomized phase II trial is studying three different schedules of gemcitabine hydrochloride and tanespimycin to see how well they work in treating patients with stage IV pancreatic cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride 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

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 Eastern Cooperative Oncology Group (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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Adenocarcinoma of the Pancreas
  • Recurrent Pancreatic Cancer
  • Stage IV Pancreatic Cancer
  • Drug: gemcitabine hydrochloride
    750 mg/m2 Given IV
    Other Names:
    • dFdC
    • difluorodeoxycytidine hydrochloride
    • gemcitabine
    • Gemzar
  • Drug: tanespimycin
    154 mg/m2 Given IV
    Other Names:
    • 17-AAG
    • 17-N-Allylamino-17-Demethoxygeldanamycin
  • Experimental: Arm I (combination chemotherapy)
    Patients receive 750 mg/m2 gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and 154 mg/m2 tanespimycin IV over 1 hour on day 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.
    Interventions:
    • Drug: gemcitabine hydrochloride
    • Drug: tanespimycin
  • Experimental: Arm II (combination chemotherapy)
    Patients receive 750 mg/m2 gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and 154 mg/m2 tanespimycin IV over 1 hour on days 2 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.
    Interventions:
    • Drug: gemcitabine hydrochloride
    • Drug: tanespimycin
  • Experimental: Arm III (combination chemotherapy)
    Patients receive 750 mg/m2 gemcitabine hydrochloride IV over 30 minutes on day 8 and 154 mg/m2 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.
    Interventions:
    • Drug: gemcitabine hydrochloride
    • Drug: tanespimycin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
May 2013
January 2011   (final data collection date for primary outcome measure)

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
  • Absolute Neutrophil Count (ANC) ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Total bilirubin normal
  • Aspartate aminotransferase (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
  • Corrected QT interval (QTc) < 500 msec
  • Pulse oximetry > 88% on room air at rest and after gentle exercise (according to Group 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)
  • 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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00577889
NCI-2009-00156, MC0542, CDR0000445454, N01CM17104
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Robert McWilliams Mayo Clinic
National Cancer Institute (NCI)
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP