ARCHER 1009 : A Study Of Dacomitinib (PF-00299804) Vs. Erlotinib In The Treatment Of Advanced Non-Small Cell Lung Cancer (ARCHER 1009)

• ClinicalTrials.gov Identifier: NCT01360554
• Recruitment Status: Completed
• First Posted: May 25, 2011
• Results First Posted: May 24, 2017
• Last Update Posted: May 24, 2017
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: April 12, 2011
• First Posted Date: May 25, 2011
• Results First Submitted Date: September 7, 2016
• Results First Posted Date: May 24, 2017
• Last Update Posted Date: May 24, 2017
• Study Start Date: June 16, 2011
• Actual Primary Completion Date: September 30, 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 24, 2017)

• Progression-Free Survival (PFS) Per Independent Radiologic Review. [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy. ]
  PFS was defined as the time from randomization to the date of disease progression as by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 per Independent Radiologic Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions.
• Progression-Free Survival (PFS) Per Independent Radiologic Review in KRAS Wild-type (WT) Participants. [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy. ]
  PFS was defined as the time from randomization to the date of disease progression as by RECIST v1.1 per Independent Radiologic Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions. Tumor tissue from participants' original diagnostic biopsies or recently obtained biopsies were analyzed to determine KRAS status.

• Original Primary Outcome Measures (submitted: May 24, 2011): Progression Free Survival per Independent Radiologic review in two co-primary populations. [ Time Frame: 10 months after anticipated LSLV ]

Current Secondary Outcome Measures (submitted: April 24, 2017)

• PFS Based on Investigator Review. [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy. ]
  PFS was defined as the time from randomization to the date of disease progression as by RECIST v1.1 per Investigator's Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions.
• PFS Based on Investigator Review in KRAS-WT Participants. [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy. ]
  PFS was defined as the time from randomization to the date of disease progression as by RECIST v1.1 per Investigator's Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions. Tumor tissue from participants' original diagnostic biopsies or recently obtained biopsies were analyzed to determine KRAS status.
• Overall Survival (OS). [ Time Frame: From date of randomization until the date of death from any cause or last date known to be alive, participants were followed up regardless of the reason for discontinuation from study treatment at intervals of no longer than every 2 months. ]
  OS was defined as the time from randomization to the date of death for any cause. In the absence of confirmation of death, survival time was censored at the last date the patient was known to be alive (ie, at their last known alive date from long term follow-up).
• OS in KRAS-WT Participants. [ Time Frame: From date of randomization until the date of death from any cause or last date known to be alive, participants were followed up regardless of the reason for discontinuation from study treatment at intervals of no longer than every 2 months. ]
  OS was defined as the time from randomization to the date of death for any cause. In the absence of confirmation of death, survival time was censored at the last date the patient was known to be alive (ie, at their last known alive date from long term follow-up). Tumor tissue from participants' original diagnostic biopsies or recently obtained biopsies were analyzed to determine KRAS status.
• Best Overall Response (BOR) Per Independent Radiologic Review. [ Time Frame: From date of randomization until progression or initiation of new anti-cancer therapy or death. Participants were followed up until progressive disease regardless of start of subsequent cancer therapy. ]
  The BOR was the best response per RECIST (version 1.1) criteria as assessed by independent assessment recorded from randomization until disease progression. Per RECIST version 1.1: Complete Response (CR): disappearance of all pre-existing lesions except nodal disease, with all nodal lesions decreased to normal size (short axis<10 mm) and no appearance of new unequivocal malignant lesions; Partial Response (PR): >=30% decrease from baseline sum of diameters of all target lesions with no unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions; Progressive Disease (PD): >=20% increase in the sum of diameters of target lesions above the smallest sum observed, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions.
• BOR Per Investigator Review. [ Time Frame: From date of randomization until progression or initiation of new anti-cancer therapy or death. Participants were followed up until progressive disease regardless of start of subsequent cancer therapy. ]
  The BOR was the best response per RECIST (version 1.1) criteria as assessed by investigator assessment recorded from randomization until disease progression. Per RECIST version 1.1: CR: disappearance of all pre-existing lesions except nodal disease, with all nodal lesions decreased to normal size (short axis<10 mm) and no appearance of new unequivocal malignant lesions; PR: >=30% decrease from baseline sum of diameters of all target lesions with no unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions; PD: >=20% increase in the sum of diameters of target lesions above the smallest sum observed, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions.
• Duration of Response (DR) Based on Independent Radiologic Review. [ Time Frame: From date of randomization until progression or death due to any cause. Participants were followed up until progressive disease regardless of start of subsequent cancer therapy. ]
  DR was defined as the time from first documentation of response assessed by independent review (CR or PR whichever occurred first) to date of progression or death due to any cause, whichever occurs first. Per RECIST version 1.1: CR: disappearance of all pre-existing lesions except nodal disease, with all nodal lesions decreased to normal size (short axis<10 mm) and no appearance of new unequivocal malignant lesions; PR: >=30% decrease from baseline sum of diameters of all target lesions with no unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions; PD: >=20% increase in the sum of diameters of target lesions above the smallest sum observed, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions.
• DR Based on Investigator Review. [ Time Frame: From date of randomization until progression or death due to any cause. Participants were followed up until progressive disease regardless of start of subsequent cancer therapy. ]
  DR was defined as the time from first documentation of response assessed by investigator review (CR or PR whichever occurred first) to date of progression or death due to any cause, whichever occurs first. Per RECIST version 1.1: CR: disappearance of all pre-existing lesions except nodal disease, with all nodal lesions decreased to normal size (short axis<10 mm) and no appearance of new unequivocal malignant lesions; PR: >=30% decrease from baseline sum of diameters of all target lesions with no unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions; PD: >=20% increase in the sum of diameters of target lesions above the smallest sum observed, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions.
• Trough Concentrations (Ctrough) of Dacomitinib. [ Time Frame: Baseline up to Cycle 5 Day 1 ]
  Mean Ctrough values of dacomitinib observed from Cycle 2 through 5, Day 1 for dose compliant participants.
• Trough Concentrations (Ctrough) of PF-05199265. [ Time Frame: Baseline up to Cycle 5 Day 1 ]
  Mean Ctrough values of PF-05199265 observed from Cycle 2 through 5, Day 1 for dose compliant participants.
• Time to Deterioration (TTD) in Pain, Dyspnea, Fatigue or Cough Patient Reported Disease Symptoms. [ Time Frame: Data taken from Cycle 1 day 1 to the end of treatment or withdrawal. ]
  TTD defined as the time from first dose (baseline) to the first time a patient's score in pain, dyspnea, fatigue or cough from the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-LC13) increased by ≥10 points. A ≥10 point increase in score had to be maintained for ≥2 consecutive cycles for the symptom to be considered deteriorated. Participants were censored at the last time when they completed an assessment for pain, dyspnea, fatigue or cough if they had not deteriorated. A 10 point or higher change in the score is perceived by participants as clinically significant.
• Mean and Difference in Mean in Functioning and Global Quality of Life (QOL) as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) [ Time Frame: Data taken from Cycle 1 day 1 to the end of treatment or withdrawal, averaged (mean) to provide overall scores. ]
  EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Scores ranged from 0-100 where a higher score indicated a better level of quality of life. Overall scores present the mean score for that scale from all time-point data.
• Mean and Difference in Mean in QLQ-C30 Symptoms as Assessed by the EORTC-QLQ-C30. [ Time Frame: Data taken from Cycle 1 day 1 to the end of treatment or withdrawal, averaged (mean) to provide overall scores. ]
  EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Scores ranged from 0-100 where a higher score indicated a greater degree of symptoms/problems. Overall scores present the mean score for that scale from all time-point data.
• Mean and Difference in Mean in Lung Cancer Symptom Scores as Assessed by the EORTC QLQ- LC13. [ Time Frame: Data taken from Cycle 1 day 1 to the end of treatment or withdrawal, averaged (mean) to provide overall scores. ]
  The QLQ-LC13 included questions specific to the disease associated symptoms (dyspnea, cough, haemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy, and alopecia), and analgesic use of lung cancer patients. Scores range from 0-100 and a higher score indicates greater degree of symptoms/problems. Overall scores present the mean score for that scale from all time-point data.
• Mean and Difference in Mean of the EuroQoL-5 Dimensions (EQ-5D) Visual Analogue Scale (VAS) Score [ Time Frame: Data taken from Cycle 1 day 1 to the end of treatment or withdrawal, averaged (mean) to provide overall scores. ]
  The EQ-5D is a validated and reliable self-report preference-based measure developed by the EuroQoL Group to assess health-related quality of life. It consists of the EQ-5D descriptive system and a visual analogue scale-the EQ VAS. The EQ-5D descriptive system measures a participants' health state on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels, reflecting "no health problems," "moderate health problems," and "extreme health problems." The EQ VAS records the respondent's self-rated health on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).

Original Secondary Outcome Measures (submitted: May 24, 2011)

• Overall Survival [ Time Frame: 12 months after anticipated LSLV ]
• Progression-Free Survival per Investigator [ Time Frame: 4 months after anticipated LSLV ]
• Best Overall Response [ Time Frame: 6 months after ]
• Duration of Response [ Time Frame: 6 months from LSLV until progression ]
• Overall Safety by CTCAE grading at each specified visit, LVEF every 3-6 months [ Time Frame: until resolution of any unresolved treatment-related adverse event for 6 months from LSLV ]
• Patient Reported Outcomes of health-related quality of life, diseases symptoms, health status [ Time Frame: 6 months from LSLV ]
• KRAS mutation status in tissue sample and HER family genotypes from serum samples at baseline [ Time Frame: baseline, and 12 months from LSLV ]
• PK trough concentrations [ Time Frame: 12 months from LSLV ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: ARCHER 1009 : A Study Of Dacomitinib (PF-00299804) Vs. Erlotinib In The Treatment Of Advanced Non-Small Cell Lung Cancer
• Official Title: Archer 1009:a Randomized, Double Blind Phase 3 Efficacy And Safety Study Of Pf-00299804 (Dacomitinib) Versus Erlotinib For The Treatment Of Advanced Non-small Cell Lung Cancer Following Progression After, Or Intolerance To, At Least One Prior Chemotherapy
• Brief Summary: This is a multinational, multicenter, randomized,double-blinded, Phase 3 study comparing the efficacy and safety of treatment with PF-00299804 to treatment with erlotinib in patients with advanced non-small cell lung cancer, previously treated with at least one prior regimen. Analyses of primary objective (Progression Free Survival) will be done in two co-primary populations as defined in the protocol.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

• Drug: Dacomitinib (PF-00299804)
  Dacomitinib (PF-00299804) is provided as 45 mg tablets, continuous oral daily dosing
• Drug: Active Comparator (erlotinib)
  Active comparator (erlotinib) provided as 150 mg tablet, continuous oral daily dosing
• Drug: Placebo erlotinib
  placebo erlotinib, provided as 150 mg tablet, continuous oral daily dosing.
• Drug: Placebo PF00299804
  placebo PF-00299804, provide as 45 mg tablet, continuous oral daily dosing

Study Arms

• Experimental: A
  Blinded active PF-00299804 + blinded placebo comparator (erlotinib)
  Interventions:

  • Drug: Dacomitinib (PF-00299804)
  • Drug: Placebo erlotinib
• Active Comparator: B
  Blinded active comparator (erlotinib) + blinded placebo PF-00299804
  Interventions:

  • Drug: Active Comparator (erlotinib)
  • Drug: Placebo PF00299804

Publications *

• Ramalingam SS, O'Byrne K, Boyer M, Mok T, Janne PA, Zhang H, Liang J, Taylor I, Sbar EI, Paz-Ares L. Dacomitinib versus erlotinib in patients with EGFR-mutated advanced nonsmall-cell lung cancer (NSCLC): pooled subset analyses from two randomized trials. Ann Oncol. 2016 Mar;27(3):423-9. doi: 10.1093/annonc/mdv593. Epub 2016 Jan 13. Erratum In: Ann Oncol. 2016 Jul;27(7):1363.
• Ramalingam SS, Janne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1369-78. doi: 10.1016/S1470-2045(14)70452-8. Epub 2014 Oct 15.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 24, 2017): 878
• Original Estimated Enrollment (submitted: May 24, 2011): 800
• Actual Study Completion Date: September 14, 2015
• Actual Primary Completion Date: September 30, 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Evidence of pathologically confirmed, advanced NSCLC (with known histology).
• Prior treatment with at least one and no more than two systemic therapy regimens (at least one must be standard chemotherapy for advanced NSCLC).
• Adequate tissue sample must be submitted prior to randomization for tumor biomarker analyses.
• Adequate renal, hematologic, liver function.
• ECOG PS of 0-2.
• Radiologically measurable disease.

Exclusion Criteria:

• Small cell histology.
• Symptomatic brain mets or known leptomeningeal mets.
• Prior therapy with agent known or proposed to be active by action on EGFR tyrosine kinase or other HER family proteins.
• Uncontrolled medical disorders.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, China, Denmark, Finland, France, Germany, Greece, Hungary, India, Ireland, Japan, Korea, Republic of, Mexico, Poland, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, United Kingdom, United States
• Removed Location Countries: Hong Kong

Administrative Information

• NCT Number: NCT01360554
• Other Study ID Numbers: A7471009; 2010-022656-22 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: April 2017