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    Summary
    EudraCT Number:2010-022656-22
    Sponsor's Protocol Code Number:A7471009
    National Competent Authority:Sweden - MPA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2011-06-23
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSweden - MPA
    A.2EudraCT number2010-022656-22
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Randomized, Double-Blind, Phase 3 Study of PF-00299804 versus Erlotinib in the Treatment of Advanced Non-Small Lung Cancer
    A.4.1Sponsor's protocol code numberA7471009
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorPfizer Inc., 235 East 42nd Street, New York, NY 10017
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportPfizer Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPfizer Inc
    B.5.2Functional name of contact pointClinical Trials.gov Call Center
    B.5.3 Address:
    B.5.3.1Street Address235 E 42nd Street
    B.5.3.2Town/ cityNew York
    B.5.3.3Post codeNY 1007
    B.5.3.4CountryUnited States
    B.5.4Telephone number+18007181021
    B.5.5Fax number+13037391119
    B.5.6E-mailClinicalTrials.govCallCenter@Pfizer.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code PF-00299804
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNdacomitinib
    D.3.9.1CAS number 1042385-75-0
    D.3.9.2Current sponsor codePF-00299804
    D.3.9.3Other descriptive nameIUPAC: 4-Piperidin-1-yl-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-7-methoxy-quinazolin-6-yl]-amide, monohydrate CAS: 2-Butenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]-7-methoxy-6-quinazolinyl]-4-(1-piperidinyl)-, monohydrate, (2E)-
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code PF-00299804
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNdacomitinib
    D.3.9.1CAS number 1042385-75-0
    D.3.9.2Current sponsor codePF-00299804
    D.3.9.3Other descriptive nameIUPAC: 4-Piperidin-1-yl-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-7-methoxy-quinazolin-6-yl]-amide, monohydrate CAS: 2-Butenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]-7-methoxy-6-quinazolinyl]-4-(1-piperidinyl)-, monohydrate, (2E)-
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code PF-00299804
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNdacomitinib
    D.3.9.1CAS number 1042385-75-0
    D.3.9.2Current sponsor codePF-00299804
    D.3.9.3Other descriptive nameIUPAC: 4-Piperidin-1-yl-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-7-methoxy-quinazolin-6-yl]-amide, monohydrate CAS: 2-Butenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]-7-methoxy-6-quinazolinyl]-4-(1-piperidinyl)-, monohydrate, (2E)-
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number45
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Tarceva®
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTarceva
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNERLOTINIB
    D.3.9.1CAS number 183321-74-6
    D.3.9.2Current sponsor codeNot Applicable
    D.3.9.3Other descriptive nameErlotinib Hydrochloride
    D.3.9.4EV Substance CodeSUB16423MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Tarceva®
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTarceva
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNERLOTINIB
    D.3.9.1CAS number 183321-74-6
    D.3.9.2Current sponsor codeNot Applicable
    D.3.9.3Other descriptive nameErlotinib Hydrochloride
    D.3.9.4EV Substance CodeSUB16423MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 6
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Tarceva®
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTarceva
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNERLOTINIB
    D.3.9.1CAS number 183321-74-6
    D.3.9.2Current sponsor codeNot Applicable
    D.3.9.3Other descriptive nameErlotinib Hydrochloride
    D.3.9.4EV Substance CodeSUB16423MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 3
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 4
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 5
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 6
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Non-small cell lung cancer
    E.1.1.1Medical condition in easily understood language
    PF-0299804 is for the potential treatment of patients with locally advanced or metastatic non-small cell lung cancer after failing of at least one prior chemotherapy regimen
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10029514
    E.1.2Term Non-small cell lung cancer NOS
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • To demonstrate that dacomitinib treatment is superior to erlotinib treatment with respect to Progression-Free Survival (PFS) in either of the co-primary populations.
    E.2.2Secondary objectives of the trial
    • To compare secondary measures of Overall Survival (OS), Objective Response and Duration of Response between arms in the co-primary populations;
    • To evaluate the safety and tolerability in each arm;
    • To compare the Patient Reported Outcomes (PRO) of health related quality of life, and disease/treatment-related symptoms between arms in the co-primary populations respectively;
    • To compare Patient Reported Outcomes (PRO) of health status between arms in the co-primary populations respectively;
    • To determine KRAS genotype, and explore HER family genotype, in tumor tissue;
    • To determine dacomitinib and PF-05199265, (O-desmethyl metabolite of dacomitinib, a major circulating metabolite in human plasma) trough concentrations (Ctrough) for the evaluation of steady-state pharmacokinetics;
    • Please refer to the protocol for a full list of secondary objectives
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study (additional details can be found in the protocol, Section 4.1):
    1. Provision of a voluntarily given, personally signed, and dated written informed consent document;
    2. Age ≥18 years, male or female;
    3. Evidence of pathologically confirmed, advanced NSCLC for which there is no curative standard therapy in the judgment of the investigator;
    a. For randomization/ stratification, the histologic subtype of NSCLC must be documented;
    b. Diagnosis of NSCLC NOS (not otherwise specified) will not be sufficient for enrollment and randomization/stratification.
    4. Specimen from archival or recently obtained tumor tissue is required, and will be sent to the Sponsor-designated central laboratory for molecular testing of tumor tissue, including KRAS mutation status, and HER family testing (as available tissue allows);
    5. ECOG 0-2 performance status;
    6. Prior treatment with at least one and no more than two regimens of systemic therapy which include at least one standard chemotherapy for advanced NSCLC;
    7. Any prior treatment (chemotherapy, radiation or surgery) must have been completed at least 2 weeks prior to randomization. Any acute toxicity related to prior therapy must have been recovered to Grade 1 (per NCI CTCAE v4) or baseline;
    8. Radiologically measurable disease by RECIST v1.1 criteria:
    a. At least one target lesion, that has not previously been radiated, and measurable as per RECIST (Appendix 4 of the protocol);
    b. Acceptable radiologic procedures for disease assessment include contrast enhanced conventional or spiral CT, or MRI; contrast enhanced scans are required in the absence of contrast-allergy and patient intolerance of MRI. The following are not allowed as sole documentation of target lesions: CT component of a Positron Emission Tomography/CT, ultrasound alone, nuclear scans (including bone or PET scans), plain CXR or bone radiographs, and tumor markers.
    9. Brain metastases treated with radiation or surgery are allowed if radiologically and neurologically stable and the subject is off corticosteroids for at least 2 weeks prior to randomization;
    10. Adequate Renal Function, including:
    a. Estimated creatinine clearance ≥15 mL/min (as determined by site’s standard formula);
    b. No known history of renal papillary necrosis or pyelonephritis.
    11. Adequate Liver Function, including:
    • Bilirubin ≤ 1.5 x upper limit of normal (ULN);
    • AST (SGOT) or ALT (SGPT) ≤ 2.5 x ULN (≤ 5.0 x ULN if hepatic metastases);
    12. Female patients or their partners must be surgically sterile or be postmenopausal (defined as 12 months of amenorrhea following last menses), or must agree to use effective contraception while receiving trial treatment and for at least 3 months thereafter. (The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. Where advised by investigator, double barrier contraception is defined as condom plus spermicide in combination with a female condom, diaphragm, cervical cap or intrauterine device).
    13. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within 72 hours prior to starting treatment.
    14. Male patients or their partners must be surgically sterile or must agree to use effective contraception while receiving trial treatment and for at least 3 months thereafter. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
    15. Patients who are willing and able to comply with study scheduled visits, treatment plans, laboratory tests, and other study procedures including patient reported measures.
    E.4Principal exclusion criteria
    1. Any evidence of mixed histology that includes elements of small cell or carcinoid lung cancer.
    2. Patients with known leptomeningeal metastases, or symptomatic brain metastases. Patients with previously diagnosed brain metastases for which treatment (radiation or surgery) is recommended in the judgment of investigator are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 2 weeks, and are neurologically stable.
    3. Chemotherapy, radiotherapy (other than palliative radiotherapy to lesions that will not be followed for tumor assessment on this study, ie, non target lesions), biological or investigational agents within 2 weeks of baseline disease assessments.
    4. Prior therapy with an agent that is known or proposed to be active by action on: EGFR tyrosine kinase or other HER family proteins including but not limited to erlotinib (Tarceva®), gefitinib (Iressa®), lapatinib (Tykerb®), cetuximab (Erbitux®), panitumumab (Vectibix®), trastuzumab (Herceptin®), ZD6474 (Zactima®), cantertinib (CI 1033), neratinib (HKI 272), Tovok (BIBW 2992), XL 647, AEE788, matuzumab, and pertuzumab.
    5. Investigational therapy as only treatment for advanced NSCLC, without administration of an approved chemotherapy for advanced NSCLC.
    6. Any surgery (not including minor procedures such as lymph node biopsy) within 2 weeks of baseline disease assessments; or not fully recovered from any side effects of previous procedures.
    7. Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drug, such as the inability to take oral medication.
    8. Current enrollment in another therapeutic clinical trial.
    9. Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this study.
    10. Patients with known diffuse interstitial lung disease.
    11. uncontrolled or significant cardiovascular disease, including:
    a. Myocardial infarction within 12 months;
    b. Uncontrolled angina within 6 months;
    c. Congestive heart failure within 6 months;
    d. Diagnosed or suspected congenital long QT syndrome;
    e. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes);
    f. Prolonged QTc interval on pre entry electrocardiogram. QTc must be less than CTC Grade 2 (≤480 msec) using Fredricia’s correction formula with manual read by investigator if required. The ECG may be repeated for evaluation of eligibility after management of correctable causes for observed QTc prolongation;
    g. Any history of second or third degree heart block (may be eligible if currently have a pacemaker);
    h. Heart rate <50/minute on baseline electrocardiogram;
    i. Uncontrolled hypertension.
    12. Prior malignancy: Patients will not be eligible if they have evidence of other malignancy (other than non melanoma skin cancer or in situ cervical cancer, or localized and presumed cured prostate cancer with Prostate Specific Antigen (PSA) < ULN) within the last 3 years.
    13. Other severe acute or chronic medical condition that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
    14. Medications are prohibited at baseline and prior to randomization if they affect the pharmacokinetics of erlotinib. For CYP2D6 substrates, drug substitution is recommended, if possible. The administration of CYP2D6 substrates requires
    consideration of the therapeutic index and the degree of CYP2D6 metabolism of the dependent CYP2D6 drug. Guidelines about administration of CYP2D6 substrates provided in the protocol.
    15.Patients who are investigational site staff members or patients who are Pfizer employees directly involved in the conduct of the trial
    E.5 End points
    E.5.1Primary end point(s)
    • Progression Free Survival (PFS) per Independent Radiologic Review in the co primary populations.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Progression Free Survival (PFS) as per the Independent Radiological Imaging Vendor – final analysis will be done approximately 10 months after anticipated LSLV. There will be periodic evaluations during the course of the study as individual patients progress (come off study treatment).
    E.5.2Secondary end point(s)
    • Overall Survival (OS);
    • Progression Free Survival (PFS) per investigator assessment;
    • Best Overall Response (BOR);
    • Duration of Response (DR).
    Overall safety profile as characterized by type, frequency, severity of adverse events as graded by NCI Common Toxicity Criteria for Adverse Events version 4 (NCI CTCAE.v4, Publish Date: 2010, http://ctep.cancer.gov/reporting/ctc.html), timing and relationship to treatment on each arm, laboratory abnormalities observed, and left ventricular imaging observed.
    Patient Reported Outcomes of health related quality of life, and disease/treatment related symptoms for patients in each arm as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30), Appendix 5, and its Lung Cancer module (QLQ LC13) Appendix 6 of the protocol.
    Patient Reported Outcomes of health status for patients in each arm as measured by the EuroQol 5 Dimension (EQ 5D) Appendix 7 of the protocol.
    KRAS and HER family genotypes in tumor tissue (fresh or archived);
    Trough concentrations (Ctrough) of dacomitinib and PF-05199265, as determined from trough plasma samples;
    Pre- and post-treatment levels in serum of protein which interact with or are part of HER family signaling pathways or escape pathways (including, but possibly not limited to, TGFalpha, EGF, amphiregulin, HGF), or proteins/peptides potentially predicting response or resistance to dacomitinib or erlotinib;
    Optional Research Components:
    Subject to IRB/IEC approval/favorable opinion, this study will include an additional research component involving collection of biological samples (whole blood and plasma) at baseline for de identified exploratory molecular profiling (“ ‘omics”) analysis. The Molecular Profiling Supplement to this protocol provides a description of this additional research. Patients may participate in the study even if they choose not to participate in this sample banking component.
    Subject to IRB/IEC approval/favorable opinion, this study will include an additional optional research component involving the collection of tissue samples at progression for exploratory biomarker studies (eg, biopsy, or thoracentesis or paracentesis for preparation of a cell block). Tumor tissue would be obtained from patients agreeing to undergo sampling procedure and who in judgment of investigator have accessible tissue and are clinically stable within 4 weeks of progression. Patients, Investigators and/or Institutions may elect not to participate in this portion of the study.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Overall Survival. Patients will be followed up until death (unless the patient is lost to follow-up).
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA78
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Austria
    Belgium
    China
    Denmark
    Finland
    France
    Germany
    Greece
    Hong Kong
    Hungary
    India
    Ireland
    Japan
    Korea, Republic of
    Mexico
    Peru
    Poland
    Russian Federation
    Slovakia
    South Africa
    Spain
    Sweden
    Switzerland
    Turkey
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    As per protocol
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 540
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 260
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Patients incapable of giving consent are only 'illiterate patients who need a legally acceptable representative signing the informed consent on their behalf'.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state16
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 350
    F.4.2.2In the whole clinical trial 800
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    This is a research study, the study drug, PF-00299804, & the study defined medical care will only be given to patients during the study, unless patients experience AEs which require appropriate follow-up.

    As stated in the protocol, for adverse events (serious/non-serious) with a causal relationship to the study drug, follow-up by the investigator is required until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, & Pfizer concurs with that assessment.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2011-07-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-08-17
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-09-14
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