Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Amino Acids

Mitogens

Dacomitinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients with NSCLC whose tumor has a documented T790M mutation in exon 20 of the Epidermal Growth Factor Receptor.

Patients with NSCLC. No requirement of a specific molecular signature, but excluding known T790M mutations.

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.

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.

Pfizer CT.gov Call Center

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.

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

Phase 2 Open Label Trial Of Oral Intermittent Dacomitinib In Patients With Advanced Nsclc

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.

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.

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.

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.

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.

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.

Cmax was observed directly from data. Whole blood for pharmacokinetic analysis was collected immediately after completion of electrocardiograms, blood pressure, and pulse rate.

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.

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.

Pfizer

Participants with documented T790M mutation in exon 20 of epidermal growth factor receptor received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle. Dose could be escalated beyond 60 mg after consultation with and approval of the sponsor.

Dacomitinib, 45/60 mg, With T790M Mutation

Participants with no known T790M mutation received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle.

Dacomitinib, 45/60 mg, Without T790M Mutation

Total

Younger than 18 years

Between 18 and 44 years

Between 45 and 64 years

65 years and older

Age, Customized

Sex: Female, Male

White

Black or African American

Asian

Other

Race/Ethnicity, Customized

All participants who received at least 1 dose of study medication.

Pfizer ClinicalTrials.gov Call Center

Complete response (CR)

Partial response (PR)

Stable disease/no response

Objective progression

Indeterminate

All enrolled participants with T790M mutation

Best Overall Response (BOR) in Participants With T790M Mutation

Disease Control Rate (DCR) for Participants With T790M Mutation

All enrolled participants with T790M mutation status who had an objective tumor response (complete or partial response)

Duration of Response in Participants With T790M Mutation

Progression-free Survival

Progression-free Survival at 4 Months

All enrolled participants with T90M mutation

Objective Response Rate (ORR) in Participants With T790M Mutation

Dacomitnib

PF-05199265 (Dacomitnib metabolite)

Participants received a 1-week lead-in cycle of dacomitinib, 45 mg, every 12 hours for 6 doses on Days 1-4.

Dacomitinib, 45 mg

All participants who received at least 1 dose of study drug and who had at least 1 measured plasma concentration of dacomitinib or its major circulating metabolite PF 05199265.

Maximum Plasma Concentration (Cmax) for Dacomitinib and PF-05199265

PF-05199265

Time to Maximum Plasma Concentration (Tmax) for Dacomitinib and PF-05199265

QTcF Interval Cycle 0, Day 4: Hour 0

QTcF Interval Cycle 0, Day 4: Hour 2

QTcF Interval Cycle 0, Day 4: Hour 4

QTcF Interval Cycle 0, Day 4: Hour 6 (n=31)

QTcF Interval Cycle 0, Day 4: Hour 8 (n=31)

QTcF Interval Cycle 0, Day 4: Hour 10 (n=31)

Participants received a 1-week lead-in cycle of dacomitinib, 45 mg, every 12 hours for 6 doses on Days 1-4. Following the lead-in cycle, all participants received intermittent dacomitinib, 60 mg, administered every 12 hours for 6 doses at the beginning of each 2-week cycle.

Dacomitinib, 45/60 mg

All participants who received all scheduled doses of dacomitinib and had all ECGs performed on Days 1-4 of Cycle 0 (n=number evaluable)

Spots Global Cancer Trial Database for A Study Of Dacomitinib (PF-00299804) In Patients With Advanced Non-Small Cell Lung Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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