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

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01858389
• Other study ID #: A7471047
• Status: Completed
• Phase: Phase 2
• First received: May 6, 2013
• Last updated: July 17, 2017
• Start date: July 2013
• Est. completion date: September 2015

Study information

• Verified date: July 2017
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

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.
• 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.

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
United States	Tower Hematology Oncology Medical Group	Beverly Hills	California
United States	UT Southwestern Medical Center	Dallas	Texas
United States	UT Southwestern Medical Center-Simmons Cancer Center Pharmacy	Dallas	Texas
United States	UT Southwestern University Hospital - William P. Clements, Jr.	Dallas	Texas
United States	UT Southwestern University Hospital - Zale Lipshy	Dallas	Texas
United States	Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California
United States	Memorial Sloan-Kettering Cancer Center-Rockefeller Outpatient Pavilion	New York	New York
United States	Investigational Drug Service, Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	UPMC 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

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Best Overall Response (BOR) in Participants With T790M Mutation	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.	From baseline until disease progression, up to 61 weeks.
Primary	Objective Response Rate (ORR) in Participants With T790M Mutation	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.	From baseline to disease progression, up to 61 weeks.
Secondary	Disease Control Rate (DCR) for Participants With T790M Mutation	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.	From baseline to baseline to disease progression, up to 61 weeks.
Secondary	Duration of Response in Participants With T790M Mutation	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.	From baseline to date of disease progression or death, up to 61 weeks.
Secondary	Progression-free Survival	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.	From baseline to disease progression or death, up to 61 weeks.
Secondary	Progression-free Survival at 4 Months	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.	Month 4
Secondary	Maximum Plasma Concentration (Cmax) for Dacomitinib and PF-05199265	Cmax was observed directly from data. Whole blood for pharmacokinetic analysis was collected immediately after completion of electrocardiograms, blood pressure, and pulse rate.	Pre-dose (hour 0), 2, 4, 6, 8, and 10 hours post-dose on Day 4, Cycle 0.
Secondary	Time to Maximum Plasma Concentration (Tmax) for Dacomitinib and PF-05199265	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.	Pre-dose (hour 0), 2, 4, 6, 8, and 10 hours post-dose on Day 4, Cycle 0.
Secondary	Changes From Time-matched Baseline in Adjusted Fridericia Corrected QT Interval (QTcF) on Echocardiogram (ECG)	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.	From Baseline to Cycle 0, Day 4

External Links

•   To obtain contact information for a study center near you, click here.