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ARCHER1050: A Study of Dacomitinib vs. Gefitinib in 1st-Line Treatment Of Advanced NSCLC. (ARCHER1050)

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ClinicalTrials.gov Identifier: NCT01774721
Recruitment Status : Active, not recruiting
First Posted : January 24, 2013
Results First Posted : October 26, 2018
Last Update Posted : October 26, 2018
Sponsor:
Collaborators:
Pfizer
SFJ Lung Cancer Ltd.
Information provided by (Responsible Party):
SFJ Pharmaceuticals, Inc.

Brief Summary:
This is a multinational, multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of treatment with dacomitinib (PF-00299804) to treatment with gefitinib in patients with locally advanced or metastatic non-small cell lung cancer, with epidermal growth factor receptor EGFR-activating mutation (s). Analyses of primary objective (Progression Free Survival) will be done as defined in the protocol.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer With EGFR-Activating Mutations Drug: Dacomitinib (PF-00299804) Drug: Gefitinib Phase 3

Detailed Description:
452 patients were randomized in a 1:1 ratio between dacomitinib (PF-00299804 ) vs. gefitinib.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 452 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: ARCHER 1050: A Randomized, Open-Label Phase 3 Efficacy and Safety Study Of Dacomitinib (PF-00299804) Vs. Gefitinib For The First-Line Treatment Of Locally Advanced or Metastatic NSCLC In Subjects With EGFR-Activating Mutations
Study Start Date : April 2013
Actual Primary Completion Date : July 2016
Estimated Study Completion Date : March 29, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Gefitinib

Arm Intervention/treatment
Experimental: Dacomitinib (PF-00299804)
Dacomitinib (PF-00299804) is provided as 45 mg tablets, continuous oral daily dosing.
Drug: Dacomitinib (PF-00299804)
Dacomitinib (PF-00299804) 45 mg tablets, continuous oral daily dosing.
Other Name: Dacomitinib

Active Comparator: gefitinib
Gefitinib is provided as 250 mg tablets, continuous oral daily dosing.
Drug: Gefitinib
Gefitinib 250 mg tablets, continuous oral daily dosing.
Other Name: Iressa




Primary Outcome Measures :
  1. Progression Free Survival (PFS) Based on Independent Radiologic Central (IRC) Review [ Time Frame: Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression or death due to any cause, whichever occurred first (up to 48 months) ]
    PFS: time from randomization to date of progression of disease (PD) as determined by IRC review as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or death due to any cause, whichever occurred first. PD for target lesions: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm; for non-target lesions: unequivocal progression of pre-existing lesions. Overall tumor burden increased sufficiently to merit discontinuation of therapy. In presence of stable disease (did not achieve partial response, complete response or PD) or partial response (>=30% decrease under baseline of sum of diameters of all target measurable lesions, short diameter used in the sum for target nodes, longest diameter used in sum for all other target lesions) in target disease; for new lesions: appearance of any new unequivocal malignant lesion indicated PD.


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) Based on Investigator Assessment [ Time Frame: Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression or death due to any cause, whichever occurred first (up to 48 months) ]
    PFS: time from randomization to date of PD as determined by investigator assessment as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or death due to any cause, whichever occurred first. PD for target lesions: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm; for non-target lesions: unequivocal progression of pre-existing lesions. Overall tumor burden increased sufficiently to merit discontinuation of therapy. In presence of stable disease (did not achieve partial response, complete response or PD) or partial response (>=30% decrease under baseline of sum of diameters of all target measurable lesions, short diameter used in the sum for target nodes, longest diameter used in sum for all other target lesions) in target disease; for new lesions: appearance of any new unequivocal malignant lesion indicated PD.

  2. Number of Participants With Best Overall Response (BOR) Based on IRC Review [ Time Frame: Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months) ]
    Number of participants with BOR based on IRC review(complete response[CR] or confirmed partial response[PR]) was recorded from randomization until disease progression based on RECISTv1.1. CR for target lesion: disappearance of all target lesions with exception of nodal disease. All target nodes must decreased to normal size(short axis <10 mm); for non-target lesions: disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be 'normal' in size(<short axis <10 mm); for new lesions: repeated assessments of a new lesion if it was equivocal. PR: >=30% decrease under baseline of sum of all target measurable lesions, short diameter was used in sum for target nodes, longest diameter was used in sum for all other target lesions. PD was defined as 20% increase in sum of 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.

  3. Number of Participants With Best Overall Response (BOR) Based on Investigator Assessment [ Time Frame: Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months) ]
    Number of participants with BOR based on investigator assessment (CR or confirmed PR) was recorded from randomization until disease progression based on RECIST v1.1. CR for target lesion: disappearance of all target lesions with exception of nodal disease. All target nodes must decreased to normal size (short axis <10 mm); for non-target lesions: disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be 'normal' in size (<short axis <10 mm); for new lesions: repeated assessments of a new lesion if it was equivocal. PR: >=30% decrease under baseline of sum of all target measurable lesions, short diameter was used in sum for target nodes, longest diameter was used in sum for all other target lesions. PD was defined as 20% increase in sum of 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.

  4. Objective Response Rate (ORR) Based on IRC Review [ Time Frame: Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months) ]
    Percentage of participants with a BOR of either CR or PR based on IRC review recorded from the start of treatment until disease progression based on RECIST v1.1. CR for target lesion: disappearance of all target lesions with exception of nodal disease. All target nodes must decreased to normal size (short axis <10 mm); for non-target lesions: disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be 'normal' in size (<short axis <10 mm); for new lesions: repeated assessments of a new lesion if it was equivocal. PR: >=30% decrease under baseline of sum of all target measurable lesions, short diameter was used in sum for target nodes, longest diameter was used in sum for all other target lesions. PD was defined as 20% increase in sum of 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.

  5. Objective Response Rate (ORR) Based on Investigator Assessment [ Time Frame: Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months) ]
    Percentage of participants with a BOR of either CR or PR based on investigator assessment recorded from the start of treatment until disease progression based on RECIST v1.1. CR for target lesion: disappearance of all target lesions with exception of nodal disease. All target nodes must decreased to normal size (short axis <10 mm); for non-target lesions: disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be 'normal' in size (<short axis <10 mm); for new lesions: repeated assessments of a new lesion if it was equivocal. PR: >=30% decrease under baseline of sum of all target measurable lesions, short diameter was used in sum for target nodes, longest diameter was used in sum for all other target lesions. PD was defined as 20% increase in sum of 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.

  6. Duration of Response (DoR) [ Time Frame: Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression or death due to any cause, whichever occurred first (up to 48 months) ]
    DoR was defined as time from first documentation of objective response(CR or PR, whichever occurred first)to date of PD or death from any cause, whichever occurred first. CR for target lesion: disappearance of all target lesions with exception of nodal disease. All target nodes decreased to normal size(short axis <10 mm); for non-target lesions: disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be 'normal' in size(<short axis <10 mm); for new lesions:repeated assessments of new lesion if it was equivocal. PR: >=30% decrease under baseline of sum of all target measurable lesions, short diameter used in sum for target nodes, longest diameter used in sum for all other target lesions. PD: 20% increase in sum of diameters of target measurable lesions above the smallest sum observed(over baseline if no decrease in sum is observed),with a minimum absolute increase of 5 mm. DoR was recorded based on IRC review and investigator's assessment.

  7. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From baseline up to 28-35 days after last dose of study drug (up to 48 months) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events between first dose of study drug and up to 28-35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non- serious adverse events.

  8. Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Haematology [ Time Frame: From baseline up to 28-35 days after last dose of study drug (up to 48 months) ]
    Laboratory parameters included haematological and biochemistry parameters. Haematology parameters included anaemia, activated partial thromboplastin time, haemoglobin, international normalized ratio, lymphocyte count, lymphopenia, neutrophils (absolute), platelets, prothrombin time and white blood cells. Biochemistry parameters included alanine aminotransferase (increased), alkaline phosphatase (increased), aspartate aminotransferase (increased), bilirubin (total), creatinine (increased), hypercalcaemia, hyperglycaemia, hyperkalaemia, hypermagnesaemia, hypernatraemia, hypoalbuminaemia, hypocalcaemia, hypoglycaemia, hypokalaemia, hypomagnesaemia, hyponatraemia. Test abnormalities were graded by AEs according to the Common Terminology Criteria for Adverse Events(NCI CTCAE) version 4.03 as Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Only categories with at least 1 participant with abnormality are reported in this outcome measure.

  9. Number of Participants With Laboratory Test Abnormalities: Urinalysis [ Time Frame: From baseline up to 28-35 days after last dose of study drug (up to 48 months) ]
    Urinalysis parameter included urine protein, urine blood/haemoglobin, urine glucose and urine sediment. Test abnormalities was defined as deviation from normal range (higher or lower). Normal range of 24-hour urine protein test: less than 150 mg of protein per day, urine glucose: 0 to 0.8 mmol/L (millimole per liter), urine protein: 0 to 20 mg/dL (milligrams per deciliter). Urine blood/haemoglobin abnormality was defined as presence and absence of blood/haemoglobin in urine of participants. Urine sediment abnormality was defined as the presence of any bacteria, casts, crystals, and epithelial cells. Only categories with at least 1 participant with abnormality are reported in this outcome measure.

  10. Number of Participants With Clinically Significant Abnormalities in Vital Signs [ Time Frame: From baseline up to 28-35 days after last dose of study drug (up to 48 months) ]
    Criteria for vital signs abnormalities: systolic pulse rate less than (<) 50 beats per minute (bpm) or greater than (>)130 bpm and maximum increase or decrease from baseline in pulse rate of 30 bpm. Systolic blood pressure of maximum increase from baseline (MIB) >=40 millimeters of mercury (mmHg), maximum decrease from baseline (MDB) in systolic blood pressure =<60 mmHg. Diastolic blood pressure of MIB >=20 mmHg and MDB in diastolic blood pressure >40 and =<20 mm Hg. Only categories with at least 1 participant with abnormality are reported in this outcome measure.

  11. Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG) [ Time Frame: From baseline up to 28-35 days after last dose of study drug (up to 48 months) ]
    ECG parameters included corrected QT interval using Bazett's formula (QTcB) and corrected QT interval using Fridericia's formula (QTcF). ECG criteria for abnormality: absolute value 450 - <480 msec, 480 - <500 msec >=500. The number of participants with potentially clinically significant ECG findings at any visit were reported.

  12. Number of Participants With Maximum Relative Decrease From Baseline >20% in Left Ventricular Ejection Fraction (LVEF) [ Time Frame: From baseline up to 7 days of Cycle 4 (up to 91 days) ]
    An ejection fraction (EF) was the volumetric fraction of blood ejected from a ventricle of the heart with each heartbeat; it was a measure of the pumping efficiency of the heart. The EF of the left heart, known as the left ventricular ejection fraction, was a measure of the efficiency of pumping into the body's systemic circulation.

  13. Health Related Quality of Life (HRQOL): Time to Deterioration (TTD) in Pain, Dyspnea, Fatigue or Cough [ Time Frame: Baseline until the end of treatment (up to 48 months) ]
    HRQOL was measured by standardized questionnaires (European Organization for Research and Treatment of Cancer (EORTC)) quality of life questionnaires (OLQ-C30) and its lung cancer module (QLQ-LC13). TTD in pain (chest, arm/shoulder), dyspnea, fatigue or cough was defined as time between baseline and first occurrence of increase in score of 10 points or greater from baseline in any of these 4 symptoms for at least two consecutive cycles. For those who had not shown deterioration, the data was censored at the last date when the participants completed an assessment for pain, dyspnea, fatigue or cough.

  14. Overall Mean Scores of Euro Quality of Life-5 Dimension Visual Analog Scale (EQ-5D VAS) [ Time Frame: From Cycle 1 to 41 (up to 48 months) ]
    The Euro Quality of Life-5 dimension (EQ-5D) is a brief self-administered, validated reliable generic health status instrument. EQ-5D general health status can also be measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).

  15. Maximum Observed Plasma Concentration (Cmax) of Dacomitinib and Its Metabolite PF-05199265 [ Time Frame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29) ]
  16. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Dacomitinib and Its Metabolite PF-05199265 [ Time Frame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29) ]
  17. Area Under the Plasma Concentration-Time Curve From Time 0 to End of Dosing Interval (AUCtau) of Dacomitinib and Its Metabolite PF-05199265 [ Time Frame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29) ]
  18. Averaged Plasma Concentration at Steady State (Cavg) of Dacomitinib and Its Metabolite PF-05199265 [ Time Frame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29) ]
  19. Minimum Observed Plasma Concentration (Cmin) of Dacomitinib and Its Metabolite PF-05199265 [ Time Frame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29) ]
  20. Fluctuation Coefficient Between Trough and Peak Plasma Concentration (DF) of Dacomitinib and Its Metabolite PF-05199265 [ Time Frame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29) ]
    Fluctuation coefficient between trough and peak plasma concentration was determined as Cmax-Ctrough divided by Cavg, where Cmax was the maximum observed concentration within the dosing interval, Ctrough was the observed concentration prior to dose administration and Cavg was averaged plasma concentration at steady state.

  21. Apparent Clearance (CL) of Dacomitinib [ Time Frame: Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29) ]
    Drug clearance was a quantitative measure of the rate at which a drug substance was removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes).

  22. Pre-dose Plasma Concentrations (Ctrough) of Dacomitinib and Its Metabolite PF-05199265 [ Time Frame: Pre-dose on Day 1 of Cycle 2, 3, 4, 5 and 6 ]
    Trough plasma concentration was defined as the measured concentration at the end of a dosing interval at steady state (taken directly before next administration).



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Evidence of histo or cytopathology confirmed, advanced NSCLC (with known histology) with the presence of EGFR-activating mutation (exon 19 deletion or the L858R mutation in exon 21).
  • It is acceptable for subjects with the presence of the exon 20 T790M mutation together with either EGFR-activating mutation (exon 19 deletion or the L858R mutation in exon 21) to be included in this study
  • Minimum of 12 months disease free interval between completion of systemic therapy and recurrence of NSCLC
  • Adequate tissue sample must be available for central analyses.
  • Adequate renal, hematologic, liver function.
  • ECOG PS of 0-1.
  • Radiologically measurable disease.

Exclusion Criteria:

  • Any evidence of mixed histology that includes elements of small cell or carcinoid lung cancer.
  • Any other mutation other than exon 19 deletion or L858R in exon 21, with or without the presence of the exon 20 T790M mutation.
  • Any history of brain mets or leptomeningeal mets.
  • Any previous anti-cancer systemic treatment of early, locally advanced, or metastatic NSCLC.
  • Uncontrolled medical disorders.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01774721


  Show 52 Study Locations
Sponsors and Collaborators
SFJ Pharmaceuticals, Inc.
Pfizer
SFJ Lung Cancer Ltd.
Investigators
Study Director: Rolf Linke, MD SFJ Pharmaceuticals, Inc.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: SFJ Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01774721     History of Changes
Other Study ID Numbers: DP312804
First Posted: January 24, 2013    Key Record Dates
Results First Posted: October 26, 2018
Last Update Posted: October 26, 2018
Last Verified: March 2018

Keywords provided by SFJ Pharmaceuticals, Inc.:
first-line
locally advanced or metastatic
non-small cell lung cancer
epidermal growth factor receptor
EGFR
ARCHER
mutation
dacomitinib
SFJ
PF-00299804

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gefitinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action