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

October 20, 2011
July 7, 2016
December 2011
May 2015   (final data collection date for primary outcome measure)
  • 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 ] [ Designated as safety issue: No ]

    SDAEI of all causality and all grades were evaluated in participants in Cohort I. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer.

    95% confidence interval (CI) calculated using exact method based on binomial distribution.

    After protocol amendment 1, Arm C was removed from Cohort I and enrollment to Arm C was terminated. Only 7 participants were enrolled in Cohort I Arm C as a result. Given the smaller sample size, analyse of Outcome Measure 1 was not conducted in Cohort I Arm C.

  • 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 ] [ Designated as safety issue: No ]

    SDAEI of all causality and Grade ≥2 were evaluated in participants in Cohort I. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer. Adverse events (AEs) were graded for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 4.0).

    95% CI calculated using exact method based on binomial distribution. After protocol amendment 1, Arm C was removed from Cohort I and enrollment to Arm C was terminated. Only 7 participants were enrolled in Cohort I Arm C as a result. Given the smaller sample size, analyse of Outcome Measure 2 was not conducted in Cohort I Arm C.

  • 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 ] [ Designated as safety issue: No ]

    Patient Reported Outcomes (PROs) of Health Related Quality of Life (HRQoL) & disease/treatment-related symptoms were assessed using Dermatologic Survey (Skindex-16) that assesses "bother". It includes 3 multi-item scales: symptoms, emotions & functioning. Individual scaled scores & total scores were determined. Skindex questions were transformed to a linear scale of 0 (never bothered) to 100 (always bothered). Subscale scores are an average of non-missing questions in a given scale if greater than (>) 75% of total subscale questions are non-missing. The Total Score is an average of all non-missing questions in the Skindex if >75% of total questions are non-missing. A negative change score represents a better quality of life. A change score of 10 points is considered clinically significant.

    Skindex completion criteria were defined as completion of 3 out of 4 items for questions 1 to 4, 6 out of 7 items for questions 5 to 11, 4 out of 5 items for questions 12 to 16 for the visit.

  • 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 ] [ Designated as safety issue: No ]

    Diarrhea AEs of all causality, all grade and Grade ≥2 were evaluated in participants in Cohort II. AEs were graded for severity using the NCI-CTCAE, Version 4.0.

    95% CI calculated using exact method based on binomial distribution.

  • 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 ] [ Designated as safety issue: No ]

    Diarrhea severity was assessed using the modified-OMDQ. This questionnaire is comprised of 6 questions in total; however, only two items relate to diarrhea symptoms (item 5 and item 6). Symptoms scores were developed for both the full questionnaire and for the diarrhea-only questions for each completed survey. Mucositis questions were transformed to a score range of 0 to 10. Increasing OMDQ values are associated with greater symptom burden.

    Modified OMDQ completion criteria were defined as completion of all 4 questions (questions 2, 4, 5 and 6).

    M/T = mouth and throat.

  • 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 ] [ Designated as safety issue: No ]

    SDAEI of all causality and all grades were evaluated in participants in Cohort II. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer.

    95% CI calculated using exact method based on binomial distribution.

  • 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 ] [ Designated as safety issue: No ]

    SDAEI of all causality and Grade ≥2 were evaluated in participants in Cohort II. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer. AEs were graded for severity using the NCI-CTCAE, Version 4.0.

    95% CI calculated using exact method based on binomial distribution.

  • 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 ] [ Designated as safety issue: No ]

    PROs of HRQoL and disease/treatment-related symptoms were assessed using Dermatologic Survey (Skindex-16) that assesses "bother". It includes 3 multi-item scales: symptoms, emotions & functioning. Individual scaled scores & total scores were determined. Skindex questions were transformed to a linear scale of 0 (never bothered) to 100 (always bothered). Subscale scores are an average of non-missing questions in a given scale if > 75% of total subscale questions are non-missing. The Total Score is an average of all non-missing questions in the Skindex if >75% of total questions are non-missing. A negative change score represents a better quality of life. A change score of 10 points is considered clinically significant.

    Skindex completion criteria were defined as completion of 3 out of 4 items for questions 1 to 4, 6 out of 7 items for questions 5 to 11, 4 out of 5 items for questions 12 to 16 for the visit.

  • 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). ] [ Designated as safety issue: No ]

    AUC0-24 is the area under the plasma concentration-time curve (AUC) from time 0 to 24 hours post-dose. AUC0-120 is the AUC from time 0 to 120 hours post-dose. AUC was calculated by the linear trapezoidal method using a non-compartmental pharmacokinetic (PK) analysis.

    ng*hr/mL = nanogram hours per milliliter

  • 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). ] [ Designated as safety issue: No ]
    Cmax was obtained from direct inspection of the data. ng/mL = nanograms per milliliter
  • 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). ] [ Designated as safety issue: No ]
    Tmax was obtained from direct inspection of the data as the time of first occurence of Cmax.
  • Cohort I: Incidence of all-causality, all grade and grade ≥2 select dermatologic adverse events of interest (SDAEI) in the first 8 weeks of treatment by arm. [ Time Frame: 10 months ] [ Designated as safety issue: No ]
  • Cohort II: Incidence of all-causality, all grade and grade ≥2 diarrhea adverse events in the first 8 weeks of treatment [ Time Frame: 4-6 months ] [ Designated as safety issue: No ]
  • Cohort I:Skindex-16 Scale scores (Total score, Symptoms score, Emotions score, Functioning score) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Cohort II:Mucositis Daily Questionaire (diarrhea questions) [ Time Frame: 10 months ] [ Designated as safety issue: No ]
  • Cohort III: Pharmacokinetics of PF-00299804 and PF-05199265 metabolite Cohort 3 primary PK endpoints include: Parent and metabolite: AUC0-120, AUC0-24, Cmax, Tmax [ Time Frame: 10 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01465802 on ClinicalTrials.gov Archive Site
  • 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) ] [ Designated as safety issue: No ]
    Medications used concomitantly for SDAEIs, diarrhea and mucositis were evaluated for all participants who received dacomitinib on a continuous basis with a preemptive prophylactic (Cohorts I and II) or as an interrupted dosing regimen (Cohort III).
  • 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 ] [ Designated as safety issue: No ]
    AUCtau was the AUC from time 0 to the end of the dosing interval, where the dosing interval was 24 hours. AUCtau was calculated by the linear/log trapezoidal method using a non-compartmental PK analysis.
  • 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 ] [ Designated as safety issue: No ]
    Cmax was obtained from direct inspection of the data.
  • 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 ] [ Designated as safety issue: No ]
    Tmax was obtained from direct inspection of the data as the time of first occurence of Cmax.
  • 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 ] [ Designated as safety issue: No ]
    CL/F was calculated as dose/AUCtau.
  • 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. ] [ Designated as safety issue: No ]

    Ctrough was the pre-dose plasma concentration of dacomitinib at steady state obtained from direct inspection of the data.

    Number of participants analyzed is the total number of participants in the treatment group in the indicated population, n is the number of participants contributing to the summary statistics.

  • 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. ] [ Designated as safety issue: No ]

    Ctrough was the pre-dose plasma concentration of the dacomitinib metabolite PF-05199265 at steady state obtained from direct inspection of the data.

    Number of participants analyzed is the total number of participants in the treatment group in the indicated population, n is the number of participants contributing to the summary statistics.

  • Overall safety profile as characterized by type, frequency, severity of adverse events as graded by NCI CTCAE.v4, timing and relationship to treatment on each arm, laboratory abnormalities observed, and left ventricular imaging observed. [ Time Frame: 14 months ] [ Designated as safety issue: Yes ]
  • Concomitant medication (both prescribed and non-prescription) used for dermatologic AEs of interest, diarrhea, and mucositis. [ Time Frame: 14 months ] [ Designated as safety issue: No ]
  • Trough concentrations (Ctrough) of PF-00299804 and PF-05199265, as determined from trough plasma samples. [ Time Frame: 10 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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: A Phase 2 Study Of Dacomitinib In Advanced Non-Small Cell Lung Cancer (Post-Chemotherapy Or Select First Line Patients) To Evaluate Prophylactic Intervention On Dermatologic And Gastrointestinal Adverse Events And Patient Reported Outcomes
To assess the impact of prophylactic treatment on the incidence of adverse events in advanced NSCLC patients (post chemotherapy) treated with dacomitinib daily as a single agent. To assess the impact of an interrupted dacomitinib dosing schedule in Cycle 1 on the incidence of adverse events in first-line advanced NSCLC patients with an EGFR mutation (HER-1 mutation, HER-2 mutation or HER-2 amplification).
Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Non Small Cell Lung Cancer (NSCLC)
  • Drug: Dacomitinib
    Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent
  • Drug: Dacomitinib
    Dacomitinib 45 mg orally daily on a continuous schedule for the first 10 days in Cycle 1, followed by 4 days off treatment, followed by continuous daily dosing until disease progression, toxicity, death or withdrawal of consent
  • Drug: Doxycycline
    Doxycycline or Doxycycline placebo BID for 4 weeks
  • Drug: Probiotic
    VSL#3 probiotic 4 capsules orally daily or 1 sachet orally daily for up to 5 weeks (starting between Day minus 7 to Day minus 4 and continuing through Day 28)
  • Drug: Alclometasone cream
    Topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks
  • Experimental: Cohort I
    Arm A: Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent Doxycycline placebo orally BID for 4 weeks Arm B: Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent Doxycycline 100 mg orally BID for 4 weeks
    Interventions:
    • Drug: Dacomitinib
    • Drug: Doxycycline
  • Experimental: Cohort II
    Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent Topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks VSL#3 probiotic 4 capsules orally daily or 1 sachet orally daily for up to 5 weeks (starting between Day minus 7 to Day minus 4 and continuing through Day 28)
    Interventions:
    • Drug: Dacomitinib
    • Drug: Probiotic
    • Drug: Alclometasone cream
  • Experimental: Cohort III
    Cohort III is an interrupted dosing schedule of dacomitinib in the first cycle only
    Intervention: Drug: Dacomitinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
236
May 2015
May 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Advanced Non-Small Cell Lung Cancer (NSCLC).
  • For Cohort I and Cohort II, advanced NSCLC patients must have received at least one prior regimen of systemic therapy which includes at least one standard chemotherapy for advanced NSCLC and who have failed (ie, progressed or intolerant due to toxicity which precludes further treatment) standard therapy for advanced or metastatic disease. To be considered intolerant to treatment, a patient must have received at least two cycles to be considered previously treated.
  • For Cohort III, advanced NSCLC patients must not have received prior systemic treatment for their advanced disease and require a known EGFR (HER-1) mutation, HER-2 mutation or HER-2 amplification. Cohort III patients could have received prior adjuvant chemotherapy for Stage I-III disease or combined modality chemotherapy-radiation for Stage IIIA disease is allowed if treatment completed>12 months prior to enrollment.
  • All cohorts, patients must have evidence of disease; however, measurable disease is not required to enroll.
  • Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
  • Estimated creatinine clearance ≥15 mL/min.

Exclusion Criteria:

  • Prior treatment with an EGFR-targeted or HER-targeted agent (all cohorts).
  • Chemotherapy, radiotherapy, biological or investigational agents within 2 weeks of baseline disease assessments (all cohorts).
  • Patients with known diffuse interstitial lung disease (all cohorts).
  • Investigational therapy as only treatment for advanced NSCLC without administration of an approved chemotherapy for advanced NSCLC (for Cohort I and Cohort II)
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Korea, Republic of
Puerto Rico
 
NCT01465802
A7471042
No
Not Provided
Not Provided
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP