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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00818441
First received: January 5, 2009
Last updated: April 25, 2016
Last verified: April 2016

January 5, 2009
April 25, 2016
March 2009
April 2012   (final data collection date for primary outcome measure)
Progression-Free Survival (PFS) at Month 4: Cohort A [ Time Frame: Baseline up to Month 4 ] [ Designated as safety issue: No ]
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.
Progression-Free survival at 4 months (PFS4m) [ Time Frame: 10 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00818441 on ClinicalTrials.gov Archive Site
  • Progression-Free Survival (PFS) at Month 4: Cohort B [ Time Frame: Baseline up to Month 4 ] [ Designated as safety issue: No ]
    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.
  • Progression-Free Survival (PFS) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.
  • Best Overall Response (BOR) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.
  • Duration of Response (DR) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.
  • Overall Survival (OS) [ Time Frame: Randomization until death or last date known to be alive. ] [ Designated as safety issue: No ]
    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).
  • European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score [ Time Frame: Baseline (Cycle [C]1 Day 1), up to C75 ] [ Designated as safety issue: No ]
    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.
  • European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score [ Time Frame: Baseline (C1D1) up to C75 ] [ Designated as safety issue: No ]
    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.
  • Trough Plasma Concentrations (Ctrough) of Dacomitinib [ Time Frame: Predose on C1D14, C2D1, C3D1, C4D1 ] [ Designated as safety issue: No ]
    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).
  • Best Overall Response (BOR) per RECIST [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Duration of Response (DR) [ Time Frame: 10 months ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Progression-free Survival (PFS) [ Time Frame: 10 months ] [ Designated as safety issue: No ]
  • Overall safety profile as characterized by type, frequency, severity as graded by NCI Common Toxicity Criteria for Adverse Events version 3.0 (NCI CTCAEv3.0), timing and relationship to treatment, and laboratory abnormalities observed; [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Patient Reported Outcomes of health related quality of life and disease/treatment-related symptoms as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and its Lung Cancer module [ Time Frame: 10 months ] [ Designated as safety issue: No ]
  • (LC13); [ Time Frame: 10 months ] [ Designated as safety issue: No ]
  • Trough concentrations of PF-00299804 in blood after repeated dosing; and concentrations of PF 00299804 in biofluid (ie, [ Time Frame: 10months ] [ Designated as safety issue: No ]
  • Exploratory endpoints: EGFR and HER signalling pathways in blood and tissue at baseline and on study [ Time Frame: 12 monhts ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Dacomitinib (PF-00299804) As A Single Oral Agent In Selected Patients With Adenocarcinoma Of The Lung
A Phase 2, Open-Label Trial Of Dacomitinib (PF-00299804) In Selected Patients With Advanced Adenocarcinoma Of The Lung
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.
Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Carcinoma, Non-small Cell
  • Drug: Dacomitinib (PF-00299804)
    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).
  • Drug: Dacomitinib (PF-00299804)
    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.
  • Experimental: Cohort A
    Dacomitinib (PF-00299804) in patients with EGFR mutated NSCLC or clinical characteristics defined above to enhance for EGFR mutated NSCLC
    Intervention: Drug: Dacomitinib (PF-00299804)
  • Experimental: Cohort B
    Dacomitinib in patients with HER2 mutated or amplified NSCLC
    Intervention: Drug: Dacomitinib (PF-00299804)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
119
April 2015
April 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Hong Kong,   Japan,   Korea, Republic of,   Taiwan
 
NCT00818441
A7471017, 2011-002794-39
No
Not Provided
Not Provided
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP