A Study Of Dacomitinib (PF-00299804) In Patients With Advanced Non-Small Cell Lung Cancer
- Registration Number
- NCT01858389
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 41
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Cohort A Dacomitinib Patients with NSCLC whose tumor has a documented T790M mutation in exon 20 of the Epidermal Growth Factor Receptor. Cohort B Dacomitinib Patients with NSCLC. No requirement of a specific molecular signature, but excluding known T790M mutations.
- Primary Outcome Measures
Name Time Method Best Overall Response (BOR) in Participants With T790M Mutation 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.
Objective Response Rate (ORR) in Participants With T790M Mutation 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
Name Time Method Disease Control Rate (DCR) for Participants With T790M Mutation 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.
Maximum Plasma Concentration (Cmax) for Dacomitinib and PF-05199265 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.
Time to Maximum Plasma Concentration (Tmax) for Dacomitinib and PF-05199265 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.
Duration of Response in Participants With T790M Mutation 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.
Progression-free Survival 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.
Progression-free Survival at 4 Months 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.
Changes From Time-matched Baseline in Adjusted Fridericia Corrected QT Interval (QTcF) on Echocardiogram (ECG) 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.
Trial Locations
- Locations (14)
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
🇺🇸Los Angeles, California, United States
Investigational Drug Service, Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Georgetown University Hospital-Lombardi Comprehensive Cancer Center
🇺🇸Washington, D.C., District of Columbia, United States
Georgetown University Medical Center Department of Pharmacy, Research
🇺🇸Washington, D.C., District of Columbia, United States
Memorial Sloan-Kettering Cancer Center-Rockefeller Outpatient Pavilion
🇺🇸New York, New York, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
UT Southwestern Medical Center-Simmons Cancer Center Pharmacy
🇺🇸Dallas, Texas, United States
Tower Hematology Oncology Medical Group
🇺🇸Beverly Hills, California, United States
UT Southwestern University Hospital - Zale Lipshy
🇺🇸Dallas, Texas, United States
UT Southwestern University Hospital - William P. Clements, Jr.
🇺🇸Dallas, Texas, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of