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A Study Of Dacomitinib (PF-00299804) In Patients With Advanced Non-Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT01858389
Recruitment Status : Completed
First Posted : May 21, 2013
Results First Posted : July 18, 2017
Last Update Posted : July 18, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
This is a Phase 2 study of oral dacomitinib given every 12 hours over days 1-4 of each two-week cycle to patients with Non-small cell lung cancer. The study includes two groups of patients, those whose tumor has a documented T790M mutation, and those without this mutation. All patients will receive repeated cycles of dacomitinib until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: Dacomitinib Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Open Label Trial Of Oral Intermittent Dacomitinib In Patients With Advanced Nsclc
Study Start Date : July 2013
Actual Primary Completion Date : September 2015
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Cohort A
Patients with NSCLC whose tumor has a documented T790M mutation in exon 20 of the Epidermal Growth Factor Receptor.
Drug: Dacomitinib
Dacomitinib 45 mg every 12 hours Days 1-4 of the first week, and then 60 mg every 12 hours Days 1-4 of each 2-week cycle thereafter. The dose of dacomitinib for patients in Cohort A may be further escalated in increments of 15 mg.
Experimental: Cohort B
Patients with NSCLC. No requirement of a specific molecular signature, but excluding known T790M mutations.
Drug: Dacomitinib
Dacomitinib 45 mg every 12 hours Days 1-4 of the first week, and then 60 mg every 12 hours Days 1-4 of each 2-week cycle thereafter.



Primary Outcome Measures :
  1. Best Overall Response (BOR) in Participants With T790M Mutation [ Time Frame: From baseline until disease progression, up to 61 weeks. ]
    BOR was best response from start of treatment until disease progression, according to the RECIST,v1.1. CR=disappearance of all preexisting 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 of sum of diameters of all target lesions with no unequivocal progression of preexisting non-target lesions or appearance of new lesions. CR and PR were confirmed on a follow-up imaging assessment ≥4 weeks after the initial response documentation. Progression= ≥20% increase in the sum of diameters of target measurable 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. Stable disease=not qualify for CR, PR or progression. BOR was analyzed only for participants with T790M mutation according to the primary study objective.

  2. Objective Response Rate (ORR) in Participants With T790M Mutation [ Time Frame: From baseline to disease progression, up to 61 weeks. ]
    ORR was calculated as the percentage of participants with a confirmed CR or PR relative to the total number of participants enrolled. Response Evaluation Criteria in Solid Tumors (RECIST), version (v) 1.1 were used to define CR and PR. CR=disappearance of all preexisting 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 of sum of diameters of all target lesions with no unequivocal progression of preexisting non-target lesions or appearance of new lesions. CR and PR were confirmed on a follow-up imaging assessment ≥4 weeks after the initial response documentation. ORR was analyzed only for participants with T790M mutation according to the primary study objective.


Secondary Outcome Measures :
  1. Disease Control Rate (DCR) for Participants With T790M Mutation [ Time Frame: From baseline to baseline to disease progression, up to 61 weeks. ]
    DCR was calculated as the percentage of participants with an objective response (CR or PR) or stable disease, based on the RECIST, v1.1, relative to the total number of participants enrolled in the cohort. If baseline tumor assessment was inadequate for a participant, and the participant could not be assessed for RECIST responses and had no objective status of stable disease documented at least 6 weeks after the start date and before the progression, the participant was only counted in the denominator. CR=disappearance of all preexisting 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 of sum of diameters of all target lesions with no unequivocal progression of preexisting non-target lesions or appearance of new lesions. DCR was analyzed only for participants with T790M mutation according to the study objective.

  2. Duration of Response in Participants With T790M Mutation [ Time Frame: From baseline to date of disease progression or death, up to 61 weeks. ]
    Duration of response was defined as the time from first documentation of response (CR or PR, whichever occurred first) to the date of disease progression or to death due to any cause, whichever occurred first. CR and PR were defined using RECIST, v1.1. CR=disappearance of all preexisting 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 of sum of diameters of all target lesions with no unequivocal progression of preexisting non-target lesions or appearance of new lesions. CR and PR were confirmed on a follow-up imaging assessment ≥4 weeks after the initial response documentation. DR was only calculated and summarized for the subgroup of participants with an objective tumor response in the cohort of participants with T790M mutation.

  3. Progression-free Survival [ Time Frame: From baseline to disease progression or death, up to 61 weeks. ]
    Progression-free survival was defined as the time from the date of first dosing of dacomitinib to the date of disease progression by RECIST v1.1, per the investigators' assessment, or death due to any cause, whichever occurred first. Objective progression= ≥20% increase in the sum of diameters of target measurable 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.

  4. Progression-free Survival at 4 Months [ Time Frame: Month 4 ]
    Progression-free survival at 4 months was defined as the percentage of participants who were alive without disease progression at 4 months relative to all participants enrolled. Disease progression was defined by RECIST v1.1. Objective progression= ≥20% increase in the sum of diameters of target measurable 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.

  5. Maximum Plasma Concentration (Cmax) for Dacomitinib and PF-05199265 [ Time Frame: Pre-dose (hour 0), 2, 4, 6, 8, and 10 hours post-dose on Day 4, Cycle 0. ]
    Cmax was observed directly from data. Whole blood for pharmacokinetic analysis was collected immediately after completion of electrocardiograms, blood pressure, and pulse rate.

  6. Time to Maximum Plasma Concentration (Tmax) for Dacomitinib and PF-05199265 [ Time Frame: Pre-dose (hour 0), 2, 4, 6, 8, and 10 hours post-dose on Day 4, Cycle 0. ]
    Tmax was observed directly from data as time of first occurrence. Whole blood for pharmacokinetic analysis was collected immediately after completion of electrocardiograms, blood pressure, and pulse rate.

  7. Changes From Time-matched Baseline in Adjusted Fridericia Corrected QT Interval (QTcF) on Echocardiogram (ECG) [ Time Frame: From Baseline to Cycle 0, Day 4 ]
    ECGs recorded on Day 1 of Cycle 0 were used as baseline. For the ECGs assessments, the following directions were followed by the ECG central laboratory: Blinding of ECG readers to treatment, time, and day identifiers. Review of ECGs from a particular participant was performed by a single reader. Prespecification of the lead for internal measurements. Baseline and on-treatment ECG assessments were based on the same lead.



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

Inclusion Criteria:

  • Evidence of histologically confirmed, advanced NSCLC (stage IIIB/IV).
  • Evidence of T790M mutation to enroll in Cohort A.
  • Evidence of measurable disease by radiographic technique.
  • Adequate organ function.

Exclusion Criteria:

  • Patients with T790M mutation who stopped any prior EGFR-directed therapy without evidence of disease progression.
  • Symptomatic brain metastases.
  • Uncontrolled or significant cardiovascular disease.
  • Pregnant or breastfeeding.

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): NCT01858389


Locations
United States, California
Tower Hematology Oncology Medical Group
Beverly Hills, California, United States, 90211
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
Los Angeles, California, United States, 90048
United States, District of Columbia
Georgetown University Hospital-Lombardi Comprehensive Cancer Center
Washington, D.C., District of Columbia, United States, 20007
Georgetown University Medical Center Department of Pharmacy, Research
Washington, D.C., District of Columbia, United States, 20007
United States, New York
Memorial Sloan-Kettering Cancer Center-Rockefeller Outpatient Pavilion
New York, New York, United States, 10022
United States, Pennsylvania
Investigational Drug Service, Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15232
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
UT Southwestern Medical Center-Simmons Cancer Center Pharmacy
Dallas, Texas, United States, 75390-9015
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
UT Southwestern University Hospital - William P. Clements, Jr.
Dallas, Texas, United States, 75390
UT Southwestern University Hospital - Zale Lipshy
Dallas, Texas, United States, 75390
Korea, Republic of
Severance Hospital, Yonsei University Health System
Seoul, Korea, Republic of, 120-752
Samsung Medical Center
Seoul, Korea, Republic of, 135-710
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01858389     History of Changes
Other Study ID Numbers: A7471047
First Posted: May 21, 2013    Key Record Dates
Results First Posted: July 18, 2017
Last Update Posted: July 18, 2017
Last Verified: July 2017

Keywords provided by Pfizer:
Non-small cell lung cancer
T790M mutation. dacomitinib

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