A Dose-Escalation to Rash Study of Tarceva (Erlotinib) Plus Gemcitabine in Patients With Metastatic Pancreatic Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00652366
First received: April 1, 2008
Last updated: January 27, 2015
Last verified: January 2015
Results First Received: December 8, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Pancreatic Cancer
Interventions: Drug: Erlotinib, escalating dose
Drug: Erlotinib, standard dose
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
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Gemcitabine (G) Plus (+) Erlotinib (E): Rash ≥ Grade 2 Participants began a 4 week run-in period where they received gemcitabine, 1000 milligrams per square meter (mg/m^2), intravenously (IV), on Days 1, 8, 15, 22 until development of a rash Grade ≥ 2. Participants also received erlotinib, 100 milligrams (mg), orally (PO) as a film-coated tablet, once daily until development of a rash Grade ≥ 2. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
G+E Standard Dose: Rash Grade Less Than (<) 2 Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
G+E Escalating Dose: Rash Grade < 2 Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 milligrams per day (mg/day), PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade ≥ 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
G+E: No Rash Non-Eligibl Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until the appearance of evidence of clinical progression or other toxicity leading to dose adjustments or discontinuation. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until the appearance of evidence of clinical progression or other toxicity leading to dose adjustments or discontinuation. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
G+E: Early Drop Out Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 for up to 4 weeks. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for up to 4 weeks.

Participant Flow:   Overall Study
    Gemcitabine (G) Plus (+) Erlotinib (E): Rash ≥ Grade 2     G+E Standard Dose: Rash Grade Less Than (<) 2     G+E Escalating Dose: Rash Grade < 2     G+E: No Rash Non-Eligibl     G+E: Early Drop Out  
STARTED     106     75     71     179     36  
COMPLETED     0     0     0     0     0  
NOT COMPLETED     106     75     71     179     36  
Adverse Event                 8                 4                 7                 17                 13  
Death                 5                 4                 1                 8                 5  
Lack of Efficacy                 84                 58                 53                 133                 13  
Violation of Selection Criteria                 0                 0                 1                 0                 0  
Protocol Violation                 1                 0                 0                 0                 0  
Refused treatment                 3                 7                 6                 17                 5  
Not specified                 5                 2                 3                 4                 0  



  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.
Safety analysis population (SAP): all participants who received at least 1 dose of the trial medication and had at least 1 safety follow-up, whether withdrawn prematurely or not.

Reporting Groups
  Description
G+E: Rash ≥ Grade 2 Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until development of a rash Grade ≥ 2. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until development of a rash Grade ≥ 2. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
G+E Standard Dose: Rash Grade < 2 Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
G+E Escalating Dose: Rash Grade < 2 Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
G+E: No Rash Non-Eligible Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until the appearance of evidence of clinical progression or other toxicity leading to dose adjustments or discontinuation. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until the appearance of evidence of clinical progression or other toxicity leading to dose adjustments or discontinuation. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
G+E: Early Drop Out Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 for up to 4 weeks. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for up to 4 weeks.
Total Total of all reporting groups

Baseline Measures
    G+E: Rash ≥ Grade 2     G+E Standard Dose: Rash Grade < 2     G+E Escalating Dose: Rash Grade < 2     G+E: No Rash Non-Eligible     G+E: Early Drop Out     Total  
Number of Participants  
[units: participants]
  106     75     70     179     36     466  
Age, Customized  
[units: participants]
           
Less Than (<) 65 Years     66     43     34     97     21     261  
≥ 65 Years     40     32     36     82     15     205  
Gender  
[units: participants]
           
Female     41     41     34     77     15     208  
Male     65     34     36     102     21     258  



  Outcome Measures
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1.  Primary:   Percentage of Participants Who Died Assessed From Point of Randomization   [ Time Frame: Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months. ]

2.  Primary:   OS Assessed From Point of Randomization   [ Time Frame: Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months. ]

3.  Secondary:   Percentage of Participants With Disease Progression or Death as Assessed From Point of Randomization   [ Time Frame: Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months. ]

4.  Secondary:   PFS Assessed From Point of Randomization   [ Time Frame: Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months. ]

5.  Secondary:   Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST   [ Time Frame: BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months. ]

6.  Secondary:   Percentage of Participants With a CR, PR, Stable Disease (SD), or PD According to RECIST   [ Time Frame: BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months. ]

7.  Secondary:   Percentage of Participants With SD (Maintained for at Least 8 Weeks) or CR or PR (Maintained for at Least 4 Weeks) According to RECIST   [ Time Frame: BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months. ]

8.  Secondary:   Percentage of Participants Who Died as Assessed From Start of 4-Week Run-In   [ Time Frame: BL and weekly thereafter for up to 46 months. ]

9.  Secondary:   OS Assessed From Start of 4-Week Run-In   [ Time Frame: BL and weekly thereafter for up to 46 months. ]

10.  Secondary:   Percentage of Participants With Disease Progression or Death as Assessed From the Start of 4-Week Run-In   [ Time Frame: BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression or death for up to 46 months. ]

11.  Secondary:   PFS Assessed From the Start of 4-Week Run-In   [ Time Frame: BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression or death for up to 46 months. ]


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


No publications provided


Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00652366     History of Changes
Other Study ID Numbers: BO21128, 2007-003751-37
Study First Received: April 1, 2008
Results First Received: December 8, 2014
Last Updated: January 27, 2015
Health Authority: Italy:National Institue of Health