Combination Chemotherapy of Gemcitabine and Paclitaxel for Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00334802
First received: June 6, 2006
Last updated: March 10, 2010
Last verified: March 2010
Results First Received: May 29, 2009  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Metastatic Breast Cancer
Interventions: Drug: gemcitabine
Drug: paclitaxel

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Dose Level 1 Gemcitabine: 1000 mg/m2, intravenous (IV), day 1 and day 8 x 2 cycles Paclitaxcel: 175 mg/m2, intravenous (IV), every 21 days x 2 cycles
Dose Level 2 Gemcitabine: 1250 mg/m2, intravenous (IV), day 1 and day 8 x 2 cycles Paclitaxcel: 175 mg/m2, intravenous (IV), every 21 days x 2 cycles

Participant Flow:   Overall Study
    Dose Level 1     Dose Level 2  
STARTED     6     56  
COMPLETED     0     16  
NOT COMPLETED     6     40  
Progressive Disease                 2                 24  
Toxicity                 1                 5  
Lack of Efficacy                 1                 3  
Patient Condition Aggrevated                 1                 0  
Physician Decision                 1                 0  
Withdrawal by Subject                 0                 4  
Adverse Event                 0                 3  
Criteria for Starting Next Cycle Not Met                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Dose Level 1 Gemcitabine: 1000 mg/m2, intravenous (IV), day 1 and day 8 x 2 cycles Paclitaxcel: 175 mg/m2, intravenous (IV), every 21 days x 2 cycles
Dose Level 2 Gemcitabine: 1250 mg/m2, intravenous (IV), day 1 and day 8 x 2 cycles Paclitaxcel: 175 mg/m2, intravenous (IV), every 21 days x 2 cycles
Total Total of all reporting groups

Baseline Measures
    Dose Level 1     Dose Level 2     Total  
Number of Participants  
[units: participants]
  6     56     62  
Age  
[units: years]
Mean ± Standard Deviation
  58.2  ± 4.49     54.4  ± 8.73     54.7  ± 8.46  
Gender  
[units: participants]
     
Female     6     56     62  
Male     0     0     0  
Region of Enrollment  
[units: participants]
     
Japan     6     56     62  
Age at Primary Diagnosis  
[units: participants]
     
<30 years old     0     0     0  
30 to <40 years old     0     3     3  
40 to <50 years old     1     20     21  
50 to <60 years old     3     24     27  
60 to <70 years old     2     8     10  
≥70 years old     0     1     1  
Eastern Cooperative Oncology Group (ECOG) Performance Status [1]
[units: participants]
     
0 - Fully Active     4     50     54  
1 - Ambulatory, Restricted Strenuous Activity     2     6     8  
Body Weight  
[units: kilograms]
Mean ± Standard Deviation
  57.18  ± 15.313     55.76  ± 8.715     55.90  ± 9.375  
Height  
[units: centimeters]
Mean ± Standard Deviation
  153.53  ± 7.987     154.71  ± 6.184     154.60  ± 6.312  
[1] Classifies patients according to their functional impairment. Scores range from 0 (Fully Active) to 5 (Death).



  Outcome Measures
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1.  Primary:   Tumor Response   [ Time Frame: baseline to measured progressive disease ]

Measure Type Primary
Measure Title Tumor Response
Measure Description Best response recorded from the start of treatment until disease progression/recurrence using Response Evaluation Criteria In Solid Tumors (RECIST) criteria that defines when participants improve ("respond"), stay the same ("stable"), or worsen ("progression") during treatment. Responders are patients with complete response or partial response.
Time Frame baseline to measured progressive disease  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Dose Level 1 Gemcitabine: 1000 mg/m2, intravenous (IV), day 1 and day 8 x 2 cycles Paclitaxcel: 175 mg/m2, intravenous (IV), every 21 days x 2 cycles
Dose Level 2 Gemcitabine: 1250 mg/m2, intravenous (IV), day 1 and day 8 x 2 cycles Paclitaxcel: 175 mg/m2, intravenous (IV), every 21 days x 2 cycles

Measured Values
    Dose Level 1     Dose Level 2  
Number of Participants Analyzed  
[units: participants]
  6     56  
Tumor Response  
[units: participants]
   
Complete Response     0     0  
Partial Response     3     25  
Stable Disease     1     17  
Progressive Disease     1     11  
Not Evaluable     1     3  


Statistical Analysis 1 for Tumor Response
Groups [1] Dose Level 1
Method [2] t-test, 2 sided
P Value [3] 0.169
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value for Dose Level 1 Responders (Complete Response + Partial Response)

Statistical Analysis 2 for Tumor Response
Groups [1] Dose Level 2
Method [2] t-test, 2 sided
P Value [3] 0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value for Dose Level 2 Responders (Complete Response + Partial Response)



2.  Secondary:   Duration of Response   [ Time Frame: time of response to progressive disease ]

Measure Type Secondary
Measure Title Duration of Response
Measure Description The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause.
Time Frame time of response to progressive disease  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Dose Level 2 Gemcitabine: 1250 mg/m2, intravenous (IV), day 1 and day 8 x 2 cycles Paclitaxcel: 175 mg/m2, intravenous (IV), every 21 days x 2 cycles

Measured Values
    Dose Level 2  
Number of Participants Analyzed  
[units: participants]
  56  
Duration of Response  
[units: months]
Median ( Full Range )
  4.70  
  ( 1.2 to 7.3 )  

No statistical analysis provided for Duration of Response



3.  Secondary:   Time to Progressive Disease   [ Time Frame: baseline to measured progressive disease ]

Measure Type Secondary
Measure Title Time to Progressive Disease
Measure Description Defined as the time from study enrollment to the first date of disease progression. Time to disease progression was censored at the date of death if death was due to other cause.
Time Frame baseline to measured progressive disease  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Dose Level 1 Gemcitabine: 1000 mg/m2, intravenous (IV), day 1 and day 8 x 2 cycles Paclitaxcel: 175 mg/m2, intravenous (IV), every 21 days x 2 cycles
Dose Level 2 Gemcitabine: 1250 mg/m2, intravenous (IV), day 1 and day 8 x 2 cycles Paclitaxcel: 175 mg/m2, intravenous (IV), every 21 days x 2 cycles

Measured Values
    Dose Level 1     Dose Level 2  
Number of Participants Analyzed  
[units: participants]
  6     56  
Time to Progressive Disease  
[units: days]
Median ( Full Range )
  310.5  
  ( 42 to 455 )  
  194.0  
  ( 29 to 265 )  

No statistical analysis provided for Time to Progressive Disease



4.  Secondary:   Number of Participants Alive at One Year (1-Year Survival)   [ Time Frame: baseline to date of death from any cause, evaluated at 1 year ]

Measure Type Secondary
Measure Title Number of Participants Alive at One Year (1-Year Survival)
Measure Description No text entered.
Time Frame baseline to date of death from any cause, evaluated at 1 year  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Dose Level 1 Gemcitabine: 1000 mg/m2, intravenous (IV), day 1 and day 8 x 2 cycles Paclitaxcel: 175 mg/m2, intravenous (IV), every 21 days x 2 cycles
Dose Level 2 Gemcitabine: 1250 mg/m2, intravenous (IV), day 1 and day 8 x 2 cycles Paclitaxcel: 175 mg/m2, intravenous (IV), every 21 days x 2 cycles

Measured Values
    Dose Level 1     Dose Level 2  
Number of Participants Analyzed  
[units: participants]
  6     56  
Number of Participants Alive at One Year (1-Year Survival)  
[units: participants]
  5     45  

No statistical analysis provided for Number of Participants Alive at One Year (1-Year Survival)



5.  Secondary:   Pharmacokinetics - Maximum Plasma Concentration (Cmax)   [ Time Frame: cycle 1, day 1 (0 minutes, 3, 3.25, 3.5, 3.58, 3.75, 4, 4.5, 5 hours) and 8 (0, 15, 30, 35, 45, 60, 90, 120 minutes) ]

Measure Type Secondary
Measure Title Pharmacokinetics - Maximum Plasma Concentration (Cmax)
Measure Description Maximum plasma concentration of gemcitabine plus paclitaxel on Day 1, Cycle 1, and gemcitabine monotherapy on Day 8, Cycle 1.
Time Frame cycle 1, day 1 (0 minutes, 3, 3.25, 3.5, 3.58, 3.75, 4, 4.5, 5 hours) and 8 (0, 15, 30, 35, 45, 60, 90, 120 minutes)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Six participants from each dose level (Dose Level 1 and Dose Level 2) were assessed for pharmacokinetic variables.

Reporting Groups
  Description
Gemcitabine + Paclitaxcel Gemcitabine: 1000 mg/m2, intravenous (IV), day 1 and day 8 or Gemcitabine: 1250 mg/m2, intravenous (IV), day 1 and day 8 Paclitaxcel: 175 mg/m2, intravenous (IV), day 1
Gemcitabine Gemcitabine: 1000 mg/m2, intravenous (IV), day 1 and day 8 or Gemcitabine: 1250 mg/m2, intravenous (IV), day 1 and day 8

Measured Values
    Gemcitabine + Paclitaxcel     Gemcitabine  
Number of Participants Analyzed  
[units: participants]
  12     12  
Pharmacokinetics - Maximum Plasma Concentration (Cmax)  
[units: nanograms per milliliter (ng/mL)]
Geometric Mean ( Full Range )
  25800  
  ( 12800 to 43600 )  
  25400  
  ( 20000 to 33100 )  

No statistical analysis provided for Pharmacokinetics - Maximum Plasma Concentration (Cmax)



6.  Secondary:   Pharmacokinetics - Area Under the Concentration Curve (AUC)   [ Time Frame: cycle 1, day 1 (0 minutes, 3, 3.25, 3.5, 3.58, 3.75, 4, 4.5, 5 hours) and 8 (0, 15, 30, 35, 45, 60, 90, 120 minutes) ]

Measure Type Secondary
Measure Title Pharmacokinetics - Area Under the Concentration Curve (AUC)
Measure Description Area under the concentration curve from time zero to infinity.
Time Frame cycle 1, day 1 (0 minutes, 3, 3.25, 3.5, 3.58, 3.75, 4, 4.5, 5 hours) and 8 (0, 15, 30, 35, 45, 60, 90, 120 minutes)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Six participants from each dose level (Dose Level 1 and Dose Level 2) were assessed for pharmacokinetic variables.

Reporting Groups
  Description
Gemcitabine + Paclitaxcel Gemcitabine: 1000 mg/m2, intravenous (IV), day 1 and day 8 or Gemcitabine: 1250 mg/m2, intravenous (IV), day 1 and day 8 Paclitaxcel: 175 mg/m2, intravenous (IV), day 1
Gemcitabine Gemcitabine: 1000 mg/m2, intravenous (IV), day 1 and day 8 or Gemcitabine: 1250 mg/m2, intravenous (IV), day 1 and day 8

Measured Values
    Gemcitabine + Paclitaxcel     Gemcitabine  
Number of Participants Analyzed  
[units: participants]
  12     12  
Pharmacokinetics - Area Under the Concentration Curve (AUC)  
[units: nanograms*hour per milliliter (ng*hr/mL)]
Geometric Mean ( Full Range )
  16300  
  ( 11700 to 25500 )  
  14700  
  ( 11500 to 21000 )  

No statistical analysis provided for Pharmacokinetics - Area Under the Concentration Curve (AUC)



7.  Secondary:   Pharmacokinetics - Half Life (t½)   [ Time Frame: cycle 1, day 1 (0 minutes, 3, 3.25, 3.5, 3.58, 3.75, 4, 4.5, 5 hours) and 8 (0, 15, 30, 35, 45, 60, 90, 120 minutes) ]

Measure Type Secondary
Measure Title Pharmacokinetics - Half Life (t½)
Measure Description Apparent elimination half-life.
Time Frame cycle 1, day 1 (0 minutes, 3, 3.25, 3.5, 3.58, 3.75, 4, 4.5, 5 hours) and 8 (0, 15, 30, 35, 45, 60, 90, 120 minutes)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Six participants from each dose level (Dose Level 1 and Dose Level 2) were assessed for pharmacokinetic variables.

Reporting Groups
  Description
Gemcitabine + Paclitaxcel Gemcitabine: 1000 mg/m2, intravenous (IV), day 1 and day 8 or Gemcitabine: 1250 mg/m2, intravenous (IV), day 1 and day 8 Paclitaxcel: 175 mg/m2, intravenous (IV), day 1
Gemcitabine Gemcitabine: 1000 mg/m2, intravenous (IV), day 1 and day 8 or Gemcitabine: 1250 mg/m2, intravenous (IV), day 1 and day 8

Measured Values
    Gemcitabine + Paclitaxcel     Gemcitabine  
Number of Participants Analyzed  
[units: participants]
  12     12  
Pharmacokinetics - Half Life (t½)  
[units: hours]
Geometric Mean ( Full Range )
  0.282  
  ( 0.192 to 1.00 )  
  0.258  
  ( 0.162 to 0.969 )  

No statistical analysis provided for Pharmacokinetics - Half Life (t½)




  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979


No publications provided


Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00334802     History of Changes
Other Study ID Numbers: 9066, B9E-JE-MB22
Study First Received: June 6, 2006
Results First Received: May 29, 2009
Last Updated: March 10, 2010
Health Authority: Japan: Ministry of Health, Labor and Welfare