Non-small Cell Lung CancerPhase 2NCT01858389
A Study Of Dacomitinib (PF-00299804) In Patients With Advanced Non-Small Cell Lung Cancer
A Phase 2 study testing Dacomitinib in people with Non-small Cell Lung Cancer, run by Pfizer at 14 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Dacomitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 14 sitesin 2 countries
- Study dates
- Jul 2013to Sep 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
14 sites in 2 countries.
14 sites in 2 countries
United States12 sites
Tower Hematology Oncology Medical Group
Beverly Hills, California, 90211
UT Southwestern Medical Center-Simmons Cancer Center Pharmacy
Dallas, Texas, 75390-9015
UT Southwestern Medical Center
Dallas, Texas, 75390
UT Southwestern University Hospital - William P. Clements, Jr.
Dallas, Texas, 75390
UT Southwestern University Hospital - Zale Lipshy
Dallas, Texas, 75390
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
Los Angeles, California, 90048
Memorial Sloan-Kettering Cancer Center-Rockefeller Outpatient Pavilion
New York, New York, 10022
Investigational Drug Service, Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Georgetown University Hospital-Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007
Georgetown University Medical Center Department of Pharmacy, Research
Washington D.C., District of Columbia, 20007
South Korea2 sites
Severance Hospital, Yonsei University Health System
Seoul, 120-752
Samsung Medical Center
Seoul, 135-710
About this study
Official title: Phase 2 Open Label Trial Of Oral Intermittent Dacomitinib In Patients With Advanced Nsclc
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.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Dacomitinib
- Keywords
- Non-small cell lung cancer, T790M mutation. dacomitinib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DacomitinibDrug
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.
DacomitinibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | Patients with NSCLC whose tumor has a documented T790M mutation in exon 20 of the Epidermal Growth Factor Receptor. Receives: Drug: Dacomitinib |
| Cohort B | Experimental | Patients with NSCLC. No requirement of a specific molecular signature, but excluding known T790M mutations. Receives: Drug: Dacomitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline until disease progression, up to 61 weeks.
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.
Measured: From baseline to disease progression, up to 61 weeks.
Secondary outcomes (7)
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.
Measured: From baseline to baseline to disease progression, up to 61 weeks.
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.
Measured: From baseline to date of disease progression or death, up to 61 weeks.
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.
Measured: From baseline to disease progression or death, up to 61 weeks.
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.
Measured: Month 4
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.
Measured: Pre-dose (hour 0), 2, 4, 6, 8, and 10 hours post-dose on Day 4, Cycle 0.
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.
Measured: Pre-dose (hour 0), 2, 4, 6, 8, and 10 hours post-dose on Day 4, Cycle 0.
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.
Measured: From Baseline to Cycle 0, Day 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2013 (estimated)
- Study startJul 2013
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01858389
- Sponsor's protocol ID
- A7471047
- Status last verified
- Jul 2017
- First submitted
- 6 May 2013
- Last updated
- 18 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Tan W, Giri N, Quinn S, Wilner K, Parivar K. Evaluation of the potential effect of dacomitinib, an EGFR tyrosine kinase inhibitor, on ECG parameters in patients with advanced non-small cell lung cancer. Invest New Drugs. 2020 Jun;38(3):874-884. doi: 10.1007/s10637-019-00887-0. Epub 2019 Dec 19.
PubMed 31858327Yu HA, Ahn MJ, Cho BC, Gerber DE, Natale RB, Socinski MA, Giri N, Quinn S, Sbar E, Zhang H, Giaccone G. Phase 2 study of intermittent pulse dacomitinib in patients with advanced non-small cell lung cancers. Lung Cancer. 2017 Oct;112:195-199. doi: 10.1016/j.lungcan.2017.08.017. Epub 2017 Aug 23.
PubMed 29191595
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Open Label Trial Of Oral Intermittent Dacomitinib In Patients With Advanced Nsclc
- ClinicalTrials.gov ID
- NCT01858389
- Acronym / sponsor ID
- A7471047
- Conditions
- Non-small Cell Lung Cancer
- Keywords
- Non-small cell lung cancer, T790M mutation. dacomitinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Jul 2013
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 21 May 2013 (estimated)
- Results
- Posted 18 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Drug: DacomitinibPatients with NSCLC whose tumor has a documented T790M mutation in exon 20 of the Epidermal Growth Factor Receptor. |
| Cohort B | Experimental | Drug: DacomitinibPatients with NSCLC. No requirement of a specific molecular signature, but excluding known T790M mutations. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DacomitinibDacomitinib 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. | Drug | Cohort A |
| DacomitinibDacomitinib 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. | Drug | Cohort B |
Primary outcome
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.
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.
7 secondary outcomes
Disease Control Rate (DCR) for Participants With T790M Mutation
Time frame: From baseline to baseline to disease progression, up to 61 weeks.
Duration of Response in Participants With T790M Mutation
Time frame: From baseline to date of disease progression or death, up to 61 weeks.
Progression-free Survival
Time frame: From baseline to disease progression or death, up to 61 weeks.
Progression-free Survival at 4 Months
Time frame: Month 4
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.
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.
Changes From Time-matched Baseline in Adjusted Fridericia Corrected QT Interval (QTcF) on Echocardiogram (ECG)
Time frame: From Baseline to Cycle 0, Day 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31858327Tan W, Giri N, Quinn S, Wilner K, Parivar K. Evaluation of the potential effect of dacomitinib, an EGFR tyrosine kinase inhibitor, on ECG parameters in patients with advanced non-small cell lung cancer. Invest New Drugs. 2020 Jun;38(3):874-884. doi: 10.1007/s10637-019-00887-0. Epub 2019 Dec 19.
- Derived from this study: PubMed 29191595Yu HA, Ahn MJ, Cho BC, Gerber DE, Natale RB, Socinski MA, Giri N, Quinn S, Sbar E, Zhang H, Giaccone G. Phase 2 study of intermittent pulse dacomitinib in patients with advanced non-small cell lung cancers. Lung Cancer. 2017 Oct;112:195-199. doi: 10.1016/j.lungcan.2017.08.017. Epub 2017 Aug 23.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
14 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dacomitinib in people with Non-small Cell Lung Cancer, run by Pfizer at 14 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best Overall Response (BOR) in Participants With T790M Mutation (time frame: From baseline until disease progression, up to 61 weeks.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01858389, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2017.