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Study Of Dacomitinib (PF-00299804) In Advanced NSCLC Patients (Post Chemo Or Select First Line) To Evaluate Prophylactic Intervention On Derm And GI AEs And PRO (ARCHER 1042)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01465802
First received: October 20, 2011
Last updated: July 7, 2016
Last verified: July 2016
Results First Received: April 15, 2016  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Non Small Cell Lung Cancer (NSCLC)
Interventions: Drug: Dacomitinib
Drug: Doxycycline
Drug: Probiotic
Drug: Alclometasone cream

  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
Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Open-label dacomitinib 45 milligram (mg) tablets orally (PO) taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline placebo capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline 100 mg capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label topical alclometasone diproprionate cream 0.05 percent (%) applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label VSL#3 probiotic 4 capsules PO taken once daily or 1 sachet PO taken once daily starting on either Days -7, -6, -5 or -4 per site/participant preference, and continuing through Cycle 1 Day 28 (for a total of up to 5 weeks [range of 32 to 35 days]) PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Cohort III (Dacomitinib 45 mg) Open-label dacomitinib 45 mg tablets PO, taken once daily Cycle 1 Day 1 through and including Cycle 1 Day 10; no dacomitinib was taken on Cycle 1 Days 11, 12, 13 and 14; resumption of dacomitinib 45 mg PO once daily taken continuously from Cycle 1 Day 15 onwards until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal.

Participant Flow:   Overall Study
    Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo)     Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg)     Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate)     Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone)     Cohort III (Dacomitinib 45 mg)  
STARTED     66     66     7     67 [1]   25  
COMPLETED     33     42     7     38     13  
NOT COMPLETED     33     24     0     29     12  
Study terminated by sponsor                 1                 0                 0                 1                 7  
Withdrawal by Subject                 7                 7                 0                 8                 1  
Lost to Follow-up                 1                 1                 0                 0                 0  
Reason not specified                 9                 4                 0                 10                 2  
Death                 15                 12                 0                 10                 2  
[1] An additional 5 participants were enrolled in Cohort II but not treated.



  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.
As Treated Population - included all participants who received at least 1 dose of study treatment assigned at enrollment.

Reporting Groups
  Description
Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline placebo capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline 100 mg capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label VSL#3 probiotic 4 capsules PO taken once daily or 1 sachet PO taken once daily starting on either Days -7, -6, -5 or -4 per site/participant preference, and continuing through Cycle 1 Day 28 (for a total of up to 5 weeks [range of 32 to 35 days]) PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Cohort III (Dacomitinib 45 mg) Open-label dacomitinib 45 mg tablets PO, taken once daily Cycle 1 Day 1 through and including Cycle 1 Day 10; no dacomitinib was taken on Cycle 1 Days 11, 12, 13 and 14; resumption of dacomitinib 45 mg PO once daily taken continuously from Cycle 1 Day 15 onwards until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal.
Total Total of all reporting groups

Baseline Measures
    Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo)     Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg)     Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate)     Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone)     Cohort III (Dacomitinib 45 mg)     Total  
Number of Participants  
[units: participants]
  66     66     7     67     25     231  
Age  
[units: Years]
Mean (Standard Deviation)
  65.0  (10.38)     64.4  (10.55)     61.3  (7.67)     66.0  (9.63)     64.2  (14.29)     64.9  (10.59)  
Gender  
[units: Participants]
           
Female     38     27     2     24     18     109  
Male     28     39     5     43     7     122  



  Outcome Measures
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1.  Primary:   Percentage of Participants With Select Dermatologic Adverse Events of Interest (SDAEI) (All Causality, All Grade) in the First 8 Weeks of Treatment by Treatment Arm for Cohort I   [ Time Frame: First 8 Weeks of Treatment ]

2.  Primary:   Percentage of Participants With SDAEI (All Causality, Grade Greater Than or Equal to [≥] 2) in the First 8 Weeks of Treatment by Treatment Arm for Cohort I   [ Time Frame: First 8 Weeks of Treatment ]

3.  Primary:   Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) by Treatment Arm for Cohort I   [ Time Frame: First 8 Weeks of Treatment ]

4.  Primary:   Percentage of Participants With Diarrhea AEs (All Causality, All Grade and Grade ≥2) in the First 8 Weeks of Treatment for Cohort II   [ Time Frame: First 8 Weeks of Treatment ]

5.  Primary:   Mean Change From Baseline (Cycle 1 Day 1) Modified Oral Mucositis Daily Questionnaire (OMDQ) Scores (Mouth and Throat Soreness Categories and Scale, and Diarrhea Categories and Scale) for Cohort II   [ Time Frame: Cycles 1, 2, 3, 4, 5, and 6, EoT and Follow-up ]

6.  Primary:   Percentage of Participants With SDAEI (All Causality, All Grade) in the First 8 Weeks of Treatment for Cohort II   [ Time Frame: First 8 Weeks of Treatment ]

7.  Primary:   Percentage of Participants With SDAEI (All Causality, Grade ≥2) in the First 8 Weeks of Treatment for Cohort II   [ Time Frame: First 8 Weeks of Treatment ]

8.  Primary:   Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II   [ Time Frame: Cycles 1, 2, 3, 4, 5, and 6, EoT and Follow-up ]

9.  Primary:   Mean Area Under the Plasma Concentration Time Curve From 0 to 24 Hours (AUC0-24) and From 0 to 120 Hours (AUC0-120) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III   [ Time Frame: Cycle 1 Day 10: Pre-dose and 2, 4, 6, 24, 48, 72, 96, and 120 hours post-dose (the 120 hour sample was obtained on Day 15 pre-dose). ]

10.  Primary:   Mean Maximum Observed Plasma Concentrations (Cmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III   [ Time Frame: Cycle 1 Day 10: Pre-dose and 2, 4, 6, 24, 48, 72, 96, and 120 hours post-dose (the 120 hour sample was obtained on Day 15 pre-dose). ]

11.  Primary:   Median Time of Occurrence of Cmax (Tmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III   [ Time Frame: Cycle 1 Day 10: Pre-dose and 2, 4, 6, 24, 48, 72, 96, and 120 hours post-dose (the 120 hour sample was obtained on Day 15 pre-dose). ]

12.  Secondary:   Percentage of Participants Receiving Any Concomitant Drug or Non-Drug Treatment for SDAEI, Diarrhea and Mucositis for Cohort I by Treatment Arm, Cohort II, and Cohort III   [ Time Frame: Screening to the Post-Teatment Follow-Up Visit (at least 28 days and no more than 35 days after the end of dacomitinib treatment due to progression of disease, intolerance to dacomitinib treatment, or participant withdrawal) ]

13.  Secondary:   Mean AUC From 0 to the End of the Dosing Interval (AUC0-tau) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I   [ Time Frame: Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose ]

14.  Secondary:   Mean Cmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I   [ Time Frame: Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose ]

15.  Secondary:   Median Tmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I   [ Time Frame: Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose ]

16.  Secondary:   Mean Apparent Clearance (CL/F) for Dacomitinib on Cycle 2 Day 1 for Cohort I   [ Time Frame: Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose ]

17.  Secondary:   Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III   [ Time Frame: Cohorts I to III: Pre-dose on Day 1 of Cycle 3 to 10. ]

18.  Secondary:   Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III   [ Time Frame: Cohorts I to III: Pre-dose on Day 1 of Cycle 3 to 10. ]


  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 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.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com



Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01465802     History of Changes
Other Study ID Numbers: A7471042
Study First Received: October 20, 2011
Results First Received: April 15, 2016
Last Updated: July 7, 2016
Health Authority: United States: Food and Drug Administration