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ATX Study:A Study of Avastin (Bevacizumab), Tarceva (Erlotinib) and Xeloda (Capecitabine) in Patients With Locally Advanced and/or Metastatic Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT00925769
Recruitment Status : Completed
First Posted : June 22, 2009
Results First Posted : August 7, 2015
Last Update Posted : August 7, 2015
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Pancreatic Cancer
Interventions: Drug: bevacizumab [Avastin]
Drug: capecitabine [Xeloda]
Drug: erlotinib [Tarceva]

  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
Thirty two (32) participants were included however, 2 participants discontinued before reaching the end of the evaluation period of 3 cycles of the complete study regimen (of all 3 drugs) at the recommended dose due to progressive disease.

Reporting Groups
  Description
ERL+BEV+CAP Dose Level-1 Participants were administered oral 100 milligrams (mg) of erlotinib (ERL) tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 milligrams per kilogram (mg/kg) of bevacizumab (BEV) intravenous (IV) infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 milligrams per square meter (mg/m^2) of capecitabine (CAP) tablet twice daily (BID) within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
ERL+BEV+CAP Dose Level-2 Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
ERL+BEV+CAP Dose Level-3 Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
ERL+BEV+CAP Dose Level-4 Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
ERL+BEV+CAP Dose Level-5 Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
ERL+BEV+CAP Dose Level-6 Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.

Participant Flow:   Overall Study
    ERL+BEV+CAP Dose Level-1   ERL+BEV+CAP Dose Level-2   ERL+BEV+CAP Dose Level-3   ERL+BEV+CAP Dose Level-4   ERL+BEV+CAP Dose Level-5   ERL+BEV+CAP Dose Level-6
STARTED   6   6   6   6   3   3 
COMPLETED   0   0   0   0   0   0 
NOT COMPLETED   6   6   6   6   3   3 
Major toxicity                1                0                1                1                0                0 
Disease progression                4                5                3                4                2                3 
Death                0                0                1                0                0                0 
Physician Decision                1                0                0                0                0                0 
Missing documentation                0                1                0                0                0                0 
End of study visit not done                0                0                1                0                0                0 
Participant is unable to swallow drug                0                0                0                1                0                0 
Adverse Event                0                0                0                0                1                0 



  Baseline Characteristics

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.
Per-protocol population: All participants who received at least 1 evaluation period of 3 cycles of the complete study regimen (of all 3 drugs) at the recommended dose unless withdrawn from therapy earlier because of toxicity.

Reporting Groups
  Description
Triple Combination (Bevacizumab/Erlotinib/Capecitabine) Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (Dose levels [DL]-1, 2, 3, 4, 5 and 6) were administered either oral 100 mg or 150 mg of erlotinib tablet daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.

Baseline Measures
   Triple Combination (Bevacizumab/Erlotinib/Capecitabine) 
Overall Participants Analyzed 
[Units: Participants]
 30 
Age 
[Units: Years]
Mean (Standard Deviation)
 63.9  (8.4) 
Gender 
[Units: Participants]
 
Female   15 
Male   15 


  Outcome Measures

1.  Primary:   Part 1: Maximum Tolerated Dose (MTD) of Capecitabine   [ Time Frame: Up to Week 6 (Cycle 1-3) ]

2.  Primary:   Part 1: MTD of Erlotinib   [ Time Frame: Up to Week 6 (Cycle 1-3) ]

3.  Primary:   Part 1: MTD of Bevacizumab   [ Time Frame: Up to Week 6 (Cycle 1-3) ]

4.  Primary:   Part 1: Preliminary Recommended Dose (PRD) of Capecitabine for Part 2   [ Time Frame: Up to Week 6 (Cycle 1-3) ]

5.  Primary:   Part 1: PRD of Erlotinib for Part 2   [ Time Frame: Up to Week 6 (Cycle 1-3) ]

6.  Primary:   Part 1: PRD of Bevacizumab for Part 2   [ Time Frame: Up to Week 6 (Cycle 1-3) ]

7.  Secondary:   Part 1: Maximum Serum Concentration (Cmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR] and 5'-Deoxy-5-Fluorouridine [5'-DFUR])   [ Time Frame: CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259) ]

8.  Secondary:   Part 1: Time to Reach Cmax (Tmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)   [ Time Frame: CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259) ]

9.  Secondary:   Part 1: Last Quantifiable Drug Concentration (Clast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)   [ Time Frame: CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259) ]

10.  Secondary:   Part 1: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)   [ Time Frame: CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259) ]

11.  Secondary:   Part 2: Percentage of Participants Free From Disease Progression   [ Time Frame: Month 6 ]

12.  Secondary:   Part 2: Percentage of Participants With Disease Control   [ Time Frame: From baseline thereafter, every 6 weeks (±7 days), then 1 week after last dose (follow-up), thereafter every 6 weeks (±7 days) until disease progression (up to Week 259) ]

13.  Secondary:   Part 2: Percentage of Participants With Clinical Benefit Response   [ Time Frame: One week before start of study treatment and weekly until disease progression or death (Up to Week 259) ]

14.  Secondary:   Part 2: Overall Survival   [ Time Frame: From baseline until death (Up to Week 259) ]


  Serious Adverse Events


  Other Adverse Events


  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
Planned Part 2 of the study was not implemented and outcome measures related to Part 2 were not analyzed.


  More Information

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: Medical Communications
Organization: Hoffmann-LaRoche
phone: 800-821-8590
e-mail: genentech@druginfo.com



Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00925769     History of Changes
Other Study ID Numbers: ML20784
2008-004444-36
First Submitted: April 15, 2009
First Posted: June 22, 2009
Results First Submitted: July 13, 2015
Results First Posted: August 7, 2015
Last Update Posted: August 7, 2015