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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
  Purpose
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).

Condition Intervention Phase
Non Small Cell Lung Cancer (NSCLC)
Drug: Dacomitinib
Drug: Doxycycline
Drug: Probiotic
Drug: Alclometasone cream
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.



Enrollment: 236
Study Start Date: December 2011
Study Completion Date: May 2015
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Dacomitinib
Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent
Drug: Doxycycline
Doxycycline or Doxycycline placebo BID for 4 weeks
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)
Drug: Dacomitinib
Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent
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 III
Cohort III is an interrupted dosing schedule of dacomitinib in the first cycle only
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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01465802

  Show 87 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
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

Keywords provided by Pfizer:
non-small cell lung cancer
advanced
previously treated

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Doxycycline
Alclometasone dipropionate
Methylprednisolone
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents

ClinicalTrials.gov processed this record on September 30, 2016