Phase III Study of ABI-007(Albumin-bound Paclitaxel) Plus Gemcitabine Versus Gemcitabine in Metastatic Adenocarcinoma of the Pancreas

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00844649
First received: February 13, 2009
Last updated: October 21, 2013
Last verified: October 2013
Results First Received: October 21, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Metastatic Pancreatic Cancer
Interventions: Drug: Albumin-bound paclitaxel
Drug: Gemcitabine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were randomized in a 1:1 ratio and the randomization was stratified by geographic region (Australia versus Eastern Europe versus Western Europe versus North America), Karnofsky performance status (70 to 80 versus 90 to 100), and by the presence of liver metastases (yes versus no)

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
38 participants were randomized but not treated due to the participants request to withdraw after the randomization results became known. 1 participant was randomized to Gemcitabine and was treated with Albumin-bound paclitaxel ABI-007/Gemcitabine in error and analyzed as treated and included in the intent to treat population (ITT)

Reporting Groups
  Description
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine (Gem) Albumin-bound paclitaxel (ABI-007)/Gemcitabine: ABI-007 125 mg/m^2 administered intravenously (IV) in combination with Gemcitabine 1000 mg/m^2 IV weekly for 3 weeks on Days 1, 8, and 15 followed by one week of rest
Gemcitabine (Gem) Gemcitabine 1000 mg/m^2 administered IV weekly for 7 weeks through Day 43 followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks on Days 1, 8, and 15 followed by a week of rest (Cycle 2 onward)

Participant Flow:   Overall Study
    Albumin-bound Paclitaxel (ABI-007)/Gemcitabine (Gem)     Gemcitabine (Gem)  
STARTED     431 [1]   430 [1]
Treated Population     421 [2]   402 [2]
COMPLETED     26 [3]   12 [3]
NOT COMPLETED     405     418  
Progressive Disease                 196                 245  
Adverse Event                 128                 73  
Physician Decision                 25                 18  
Protocol Violation                 10                 6  
Withdrawal by Subject                 28                 39  
Unspecified                 7                 10  
Withdrew prior to starting treatment                 11                 27  
[1] Started = Intent to Treat Population and includes all randomized participants
[2] Treated population = all randomized patients who received at least one dose of study drug
[3] Completed = participants remaining on treatment at the time of the data cut off 17 Sept 2012



  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.
For the KPS baseline characteristic, some of the participants did not have a baseline KPS recorded by the clinical site.

Reporting Groups
  Description
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine

ABI-007 125 mg/m^2 administered in combination with gemcitabine 1000 mg/m^2 weekly for 3 weeks followed by one week of rest.

Albumin-bound paclitaxel (ABI-007)/Gemcitabine : ABI-007 125 mg/m^2 administered in combination with Gemcitabine 1000 mg/m^2 weekly for 3 weeks, Days 1, 8, and 15 followed by one week of rest

Gemcitabine

Gemcitabine, 1000 mg/m^2 administered weekly for 7 weeks followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks followed by a week of rest (Cycle 2 onward).

Gemcitabine : Gemcitabine, 1000 mg/m2 administered weekly for 7 weeks, Day 1 through Day 43 followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks, Days 1, 8, and 15 followed by a week of rest (Cycle 2 onward).

Total Total of all reporting groups

Baseline Measures
    Albumin-bound Paclitaxel (ABI-007)/Gemcitabine     Gemcitabine     Total  
Number of Participants  
[units: participants]
  431     430     861  
Age  
[units: years]
Mean ± Standard Deviation
  61.4  ± 10.70     63.0  ± 9.27     62.2  ± 10.04  
Gender  
[units: participants]
     
Female     186     173     359  
Male     245     257     502  
Race (NIH/OMB)  
[units: participants]
     
American Indian or Alaska Native     0     0     0  
Asian     8     9     17  
Native Hawaiian or Other Pacific Islander     1     0     1  
Black or African American     16     16     32  
White     378     375     753  
More than one race     25     26     51  
Unknown or Not Reported     3     4     7  
Karnofsky Performance Status (KPS) [1]
[units: participants]
     
100% = normal, no complaints, no signs of disease     69     69     138  
90% = normal activity, few symptoms of disease     179     199     378  
80% = normal activity, some symptoms of disease     149     128     277  
70% = caring for self, unable to work     30     33     63  
60% = needs help, can manage most tasks     2     0     2  
50% = needs help often and medical care     0     0     0  
40% = disabled; requires special care & assistance     0     0     0  
30% = severely disabled; death is imminent     0     0     0  
20% = hospitalized; requires supportive treatment     0     0     0  
10% = Moribund, fatal processes progressing fast     0     0     0  
0% = Dead     0     0     0  
Pancreatic Primary Tumor Location [2]
[units: participants]
     
Head     191     180     371  
Body     132     136     268  
Tail     105     110     215  
Unknown = not specified     3     4     7  
Number of Baseline Lesions (Target + Non-Target) [3]
[units: participants]
     
1     1     0     1  
2     32     25     57  
3     7     7     14  
4     37     43     80  
5     8     8     16  
>5     276     262     538  
[1] The Karnofsky Performance Status Scale (KPS) was designed to measure the level of participant activity and medical care requirements. A general measure of participant independence and has been widely used as a general assessment of participants with cancer. The Karnofsky score runs from 100 to 0, where 100 is "perfect" health and 0 is death. The primary purpose of its development was to allow physicians to evaluate a participant's ability to survive chemotherapy for cancer. Two participants from the Albumin bound paclitaxel arm and one from the Gemcitabine arm did not have KPS performed.
[2] Main location or area of the pancreas where the disease is detected at diagnosis. Unknown location refers to disease area not being specified.
[3] Target lesions are those measurable at baseline and are generally the largest lesions, most reliably measured and most representative of the participants sites of disease. Non target lesions are all of the sites of disease present at baseline not classified as target lesions. They include bone and cystic lesions and pleural/pericardial effusion/ascites. The Independent Radiology Reviewers (IRR) only evaluated scans for those with baseline and follow-up scans.



  Outcome Measures
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1.  Primary:   Overall Survival (OS)   [ Time Frame: From randomization to death; until the data cut off 17 Sept 2012. The maximum time in follow up was 37 months. ]

2.  Secondary:   Progression-free Survival (PFS) by Independent Radiological Review (IRR)   [ Time Frame: Randomization until disease progression or death from any cause; Until the data cut off of 17 Sept 2012. The maximum time in follow up was 37 months. ]

3.  Secondary:   Percentage of Participants Who Achieved an Objective Confirmed Overall Response by Independent Radiological Review (IRR)   [ Time Frame: Assessment every 4 weeks after initial response; Day 1 to data cut off of 17 Sept 2013; maximum time on study 37 months ]
  Hide Outcome Measure 3

Measure Type Secondary
Measure Title Percentage of Participants Who Achieved an Objective Confirmed Overall Response by Independent Radiological Review (IRR)
Measure Description Objective tumor response was summarized as the percentage of participants who achieved a confirmed complete (CR) or partial response (PR) based on an independent blinded radiology assessment of response using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Using RECIST Version 1.0, participants were to achieve either a complete response (CR) defined as the disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation or partial response (PR) defined as at least a 30% decrease in the sum of the longest diameters of target lesions and no progression in non-target lesions based on confirmed responses from the investigator assessment of best overall response during study treatment.
Time Frame Assessment every 4 weeks after initial response; Day 1 to data cut off of 17 Sept 2013; maximum time on study 37 months  
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.
ITT Population

Reporting Groups
  Description
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine Albumin-bound paclitaxel (ABI-007)/Gemcitabine: ABI-007 125 mg/m^2 administered intravenously (IV) in combination with Gemcitabine 1000 mg/m^2 IV weekly for 3 weeks on Days 1, 8, and 15 followed by one week of rest
Gemcitabine Gemcitabine 1000 mg/m^2 administered IV weekly for 7 weeks through Day 43 followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks on Days 1, 8, and 15 followed by a week of rest (Cycle 2 onward)

Measured Values
    Albumin-bound Paclitaxel (ABI-007)/Gemcitabine     Gemcitabine  
Number of Participants Analyzed  
[units: participants]
  431     430  
Percentage of Participants Who Achieved an Objective Confirmed Overall Response by Independent Radiological Review (IRR)  
[units: percentage¬†of¬†participants]
Number ( 95% Confidence Interval )
  23  
  ( 19.1 to 27.2 )  
  7  
  ( 5.0 to 10.1 )  


Statistical Analysis 1 for Percentage of Participants Who Achieved an Objective Confirmed Overall Response by Independent Radiological Review (IRR)
Groups [1] All groups
Method [2] Chi-squared
P Value [3] <0.0001
Response Rate Ratio [4] 3.19
95% Confidence Interval ( 2.178 to 4.662 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  PA+G/PG = response rate ratio of albumin bound paclitaxel + gemcitabine / gemcitabine.
[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:
  No text entered.
[4] Other relevant estimation information:
  Response rate ratio: albumin-bound paclitaxel + gemcitabine /gemcitabine alone



4.  Other Pre-specified:   Participants With Treatment Emergent Adverse Events (AE)   [ Time Frame: Study drug initiation through 30 days after the last dose of study drug or EOS, whichever is later; Up to 696 days ]

5.  Other Pre-specified:   Number of Participants With Dose Reductions   [ Time Frame: Maximum time on treatment was 666 days ]

6.  Other Pre-specified:   Number of Participants With Dose Interruptions   [ Time Frame: Maximum time on treatment was 666 days ]

7.  Other Pre-specified:   Number of Participants With Dose Delays/Doses Not Given   [ Time Frame: Up to 666 days ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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.


  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 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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Anne McClain
Organization: Celgene Corporation
phone: 1-888-260-1599
e-mail: clinicaltrialdisclosure@celgene.com


No publications provided by Celgene Corporation

Publications automatically indexed to this study:

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00844649     History of Changes
Other Study ID Numbers: CA046
Study First Received: February 13, 2009
Results First Received: October 21, 2013
Last Updated: October 21, 2013
Health Authority: United States: Food and Drug Administration
Russia: Ministry of Health of the Russian Federation
Ukraine: Ministry of Health
Italy: The Italian Medicines Agency
Canada: Health Canada
Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Spain: Spanish Agency of Medicines
Australia: Department of Health and Ageing Therapeutic Goods Administration