Dacomitinib (PF-00299804) As A Single Oral Agent In Selected Patients With Adenocarcinoma Of The Lung
- Registration Number
- NCT00818441
- Lead Sponsor
- Pfizer
- Brief Summary
This study will explore the safety and efficacy of the oral PanHER inhibitor PF-00299804 in patients with adenocarcinoma of the lung who are either non-smokers (\<100 cigarette, cigar or pipe lifetime) or former light smokers ( less than 10 pack-years and stopped at least 15 years) or have known EGFR activating mutation; or patients with HER 2 amplification or mutation.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 119
- Advanced adenocarcinoma of lung, measurable disease
- Non-smoker, or former light (less than 10 pack years and stopped at least 15 years); OR
- patients with known EGFR activating mutation regardless of smoking status
- ECOG(Eastern Cooperative Oncology Group) 0-1.
Cohort B (select sites only): patients with HER2 amplified or HER2 mutation-positive NSCLC; may have had prior therapy
- Active brain metastases
- Prior systemic therapy for advanced disease in Cohort A only. Cohort B can have had any number of prior lines of systemic therapy.
- known EGFR wild type NSCLC
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Cohort B Dacomitinib (PF-00299804) Dacomitinib in patients with HER2 mutated or amplified NSCLC Cohort A Dacomitinib (PF-00299804) Dacomitinib (PF-00299804) in patients with EGFR mutated NSCLC or clinical characteristics defined above to enhance for EGFR mutated NSCLC
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) at Month 4: Cohort A Baseline up to Month 4 PFS at Month 4 was defined as percentage of participants who were alive and event free (event defined as progressive disease \[PD\] or death due to any cause, whichever occurs first) at 4 months after the first dose of study treatment. Documentation of progression was based on Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) criteria. PD = greater than or equal to (\>=) 20 percent (%) increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the start of treatment, or the appearance of 1 or more new lesions, or unequivocal progression in non-target lesions.
- Secondary Outcome Measures
Name Time Method Best Overall Response (BOR) Baseline until progression or initiation of new anti-cancer therapy or death, assessed at baseline, at the end of Cycle 1, Cycle 2, and then every other cycle. BOR: best response recorded from treatment start until disease progression/recurrence based on RECIST v1.0. Complete Response (CR): disappearance of all lesions. Partial Response (PR): \>=30% decrease in sum of longest diameters of target lesions taking as reference baseline sum of longest diameters, associated to non-progressive disease response for non target lesions. PD: \>=20% increase in sum of longest diameters of target lesions taking as reference smallest sum of longest diameters since treatment start, or appearance of \>=1 new lesion, or unequivocal progression in non-target lesions. Stable disease (SD): neither shrinkage for CR/PR nor increase for PD taking as reference smallest sum of longest diameters since treatment start. CR and PR had to be confirmed on a follow up imaging assessment \>=4 weeks after the initial objective documentation of the response. SD must have met the SD criteria at least once after start of treatment in a minimum interval of 6 weeks.
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Baseline (Cycle [C]1 Day 1), up to C75 EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status (GHS), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Most questions used 4- point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). For GHS, functional scales, symptom scales and single items, scores were averaged, transformed to 0-100 scale; higher score=better level of functioning/health or greater degree of symptoms. Improvement was defined as a mean increase from baseline of ≥10 for GHS and functional scales or a mean decrease from baseline of ≤10 for symptom scales. Worsened was defined as a mean decrease from baseline of ≤10 for GHS and functional scales or a mean increase from baseline of ≥10 for symptom scales. Stable was a mean change from baseline of \<10.
Progression-Free Survival (PFS) Baseline until progression or initiation of new anti-cancer therapy or death, assessed at baseline, at the end of Cycle 1, Cycle 2, and then every other cycle. PFS was defined as the time in months from the first dosing date to the date of first documentation of progression or death due to any cause, whichever occurs first. PFS was calculated as (first event date \[if not reached, censored date as the last known event-free date\] minus first dosing date plus 1) divided by 30.44. PD: \>= 20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the start of treatment, or the appearance of 1 or more new lesions. Documentation of progression was determined from objective disease assessment based on RECIST v1.0 criteria.
Duration of Response (DR) Baseline until progression or initiation of new anti-cancer therapy or death, assessed at baseline, at the end of Cycle 1, Cycle 2, and then every other cycle. Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause, whichever occurs first. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to any cause \[if not reached, censored date\] minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.44. DR was calculated for a subgroup of participants with a confirmed objective tumor response.
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Baseline (C1D1) up to C75 QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain ). Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results are reported for coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, and other pain. Improvement was defined as a mean decrease from baseline of ≤10. Worsened was defined as a mean increase from baseline of ≥10. Stable was a mean change from baseline of \<10.
Progression-Free Survival (PFS) at Month 4: Cohort B Baseline up to Month 4 PFS at Month 4 was defined as percentage of patients who were alive and event free (event defined as PD or death due to any cause, whichever occurs first) at 4 months after the first dose of study treatment. Documentation of progression was based on RECIST v1.0 criteria. PD: \>=20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the start of treatment, or the appearance of 1 or more new lesions, or unequivocal progression in non-target lesions.
Overall Survival (OS) Randomization until death or last date known to be alive. Time in months from the start of study treatment to date of death due to any cause. OS was calculated as (the death date or last alive date minus the date of first dose of study medication plus 1) divided by 30.44. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).
Trough Plasma Concentrations (Ctrough) of Dacomitinib Predose on C1D14, C2D1, C3D1, C4D1 Results for Ctrough were summarized as per the dose received during given cycle: no dose (treatment interruption at any cycle due to treatment-related toxicity), dacomitinib 15 mg (dacomitinib 15 mg at any cycle due to treatment-related toxicity at higher doses), 30 mg (dacomitinib 30 mg at any cycle as starting dose or dose reduction due to treatment-related toxicity at higher doses), 45 mg (dacomitinib 45 mg at any cycle as starting dose or dose escalation due to satisfactory toleration of dacomitinib 30 mg treatment).
Trial Locations
- Locations (36)
St. John's Hospital,
🇺🇸Springfield, Missouri, United States
Stony Brook University Medical Center - Cancer Center
🇺🇸Stony Brook, New York, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
National Institutes of Health National Cancer Institute
🇺🇸Bethesda, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Brigham & Women's Hospital
🇺🇸Boston, Massachusetts, United States
Mid Dakota Clinic, P.C
🇺🇸Bismarck, North Dakota, United States
The Cancer Institute Hospital of JFCR
🇯🇵Koto-Ku, Tokyo, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Florida Cancer Specialists
🇺🇸Fort Myers, Florida, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Prince of Wales Hospital
🇭🇰Shatin, NT, Hong Kong
SamsungMedicalCenter, Sungkyunkwan Univ School of Medicine
🇰🇷Seoul, Korea, Republic of
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
University of California, Irvine
🇺🇸Orange, California, United States
Bay Area Cancer Research Group, LLC
🇺🇸Pleasant Hill, California, United States
Investigational Drug Service, Pharmacy Department, UNC Hospitals
🇺🇸Chapel Hill, North Carolina, United States
San Francisco General Hospital
🇺🇸San Francisco, California, United States
Pacific Cancer Care
🇺🇸Salinas, California, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Morris Cancer Center
🇺🇸Durham, North Carolina, United States
Division of Hemotology/Oncology
🇺🇸Chapel Hill, North Carolina, United States
Virginia Cancer Institute
🇺🇸Richmond, Virginia, United States
Chao Family Comprehensive Cancer Center UC Irvine Medical Center
🇺🇸Orange, California, United States
University of Colorado Clinical Trials Office (CTO)
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Dana-Farber Cancer lnstitute
🇺🇸Boston, Massachusetts, United States
UNC Hospitals, The University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Legacy Pharma Research
🇺🇸Bismarck, North Dakota, United States
Severance Hospital, Yonsei University College of Medicine, Yonsei Cancer Center
🇰🇷Seoul, Korea, Republic of
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Chattanooga Oncology & Hematology Associates, P.C.
🇺🇸Chattanooga, Tennessee, United States
Aichi cancer center central hospital Thoracic Oncology
🇯🇵Aichi, Japan
Department of Clinical Oncology, Tuen Mun Hospital
🇭🇰New Territories, Hong Kong