Dacomitinib (PF-00299804) As A Single Oral Agent In Selected Patients With Adenocarcinoma Of The Lung

Study Overview
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Brief Summary
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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.

Official Title
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A PHASE 2, OPEN-LABEL TRIAL OF DACOMITINIB (PF-00299804) IN SELECTED PATIENTS WITH ADVANCED ADENOCARCINOMA OF THE LUNG

Conditions
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Carcinoma, Non-small Cell

Intervention / Treatment
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* Drug: Dacomitinib (PF-00299804)
* Drug: Dacomitinib (PF-00299804)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>Dacomitinib (PF-00299804) in patients with EGFR mutated NSCLC or clinical characteristics defined above to enhance for EGFR mutated NSCLC | Drug: Dacomitinib (PF-00299804)<br>* Dacomitinib (PF-00299804) at 45 mg daily or 30 mg daily by continuous oral dosing, to be escalated in tolerating patients to 45mg after at least 8 weeks of therapy (30 patients in Cohort A started at the lower dose).<br>|
| Experimental: Cohort B<br>Dacomitinib in patients with HER2 mutated or amplified NSCLC | Drug: Dacomitinib (PF-00299804)<br>* In Cohort B, patients getting Dacomitinib for first line therapy started at 30 mg, but those who had prior anti-cancer therapy started at 45 mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) at Month 4: Cohort A | 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. | Baseline up to Month 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) at Month 4: Cohort B | 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. | Baseline up to Month 4 | 
| Progression-Free Survival (PFS) | 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. | 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. | 
| Best Overall Response (BOR) | 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. | 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. | 
| Duration of Response (DR) | 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. | 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. | 
| Overall Survival (OS) | 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). | Randomization until death or last date known to be alive. | 
| European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score | 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. | Baseline (Cycle [C]1 Day 1), up to C75 | 
| European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score | 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. | Baseline (C1D1) up to C75 | 
| Trough Plasma Concentrations (Ctrough) of Dacomitinib | 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). | Predose on C1D14, C2D1, C3D1, C4D1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung cancer adenocarcinoma HER2