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A Randomized Trial Of PF-00299804 Taken Orally Versus Erlotinib Taken Orally For Treatment Of Advanced Non-Small Cell Lung Cancer That Has Progressed After One Or Two Prior Chemotherapy Regimen

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ClinicalTrials.gov Identifier: NCT00769067
Recruitment Status : Completed
First Posted : October 8, 2008
Results First Posted : August 21, 2015
Last Update Posted : October 7, 2015
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE October 7, 2008
First Posted Date  ICMJE October 8, 2008
Results First Submitted Date  ICMJE July 27, 2015
Results First Posted Date  ICMJE August 21, 2015
Last Update Posted Date October 7, 2015
Study Start Date  ICMJE November 2008
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 27, 2015)
Progression-Free Survival (PFS) [ Time Frame: Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks ]
PFS: Time in weeks from randomization to date of objective disease progression or death due to any cause, whichever occurred first. PFS was calculated as (first event date or last known event-free date [if the event date unavailable] minus the date of randomization plus 1) divided by 7. Objective progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST), as at least 20 percent (%) increase in the sum of longest dimensions (LDs) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Original Primary Outcome Measures  ICMJE
 (submitted: October 7, 2008)
Progression- Free Survival for patients in each arm [ Time Frame: 13 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2015)
  • Categorical Summary of Overall Scale Change in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) [ Time Frame: Baseline up to Cycle 44 (Week 188) ]
    EORTC QLQ-C30: included global health status/quality of life (QoL), functional (Fn) scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Scores were averaged, transformed to 0-100 scale; higher score for Global Qol/Fn scales=better level of QoL/functioning or higher score for symptom scales/items=greater degree of symptoms. Overall scale change is categorized as Improved (if average scales change from baseline: for Global QoL/Fn scales >=10; for symptom scale/item <=-10), Worsened (if average scales change from baseline: for Global QoL/Fn scales <=-10; for symptom scale/item >=10), and Stable (if average scales change from baseline >-10 but <10 for Global QoL/Fn scales and symptom scale/item) and participants in each category are reported.
  • Categorical Summary of Overall Scale Change in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) [ Time Frame: Baseline up to Cycle 44 (Week 188) ]
    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. 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). Scores averaged, transformed to 0-100 scale; higher symptom score = greater degree of symptoms. Overall scale change is categorized as Improved (if average scales change from baseline <=-10), Worsened (if average scales change from baseline >=10), and Stable (if average scales change from baseline >-10 but <10) and participants in each category are reported.
  • Dermatology Life Quality Index (DLQI) [ Time Frame: Cycle (C) 1 Day (D) 1 (baseline), C1D10-14, D1 of subsequent cycles up to C44 ]
    DLQI: 10-item questionnaire to measure how much the participant's skin problem has impacted their life over the previous week on following 6 domains: symptoms/feelings (2 questions), daily activities (2 questions), leisure (2 questions), work/school (1 question), personal relationships (2 questions), and treatment (1 question). All questions were answered on a 4-point Likert scale ranging from 0 (not at all/not relevant) to 3 (very much/prevented work or studying). The DLQI total evaluable score was calculated by summing the score of each question and ranged from 0 to 30, where higher scores indicated more quality of life impairment.
  • Percentage of Participants With Objective Response [ Time Frame: Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks ]
    Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.0. CR: disappearance of all target and non-target lesions. PR: at least 30 % decrease in sum of the LDs of target lesion, taking as reference the baseline sum LD. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response.
  • Best Overall Response (BOR) [ Time Frame: Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks ]
    Number of participants with BOR according to RECIST version 1.0: CR= disappearance of all target and non-target lesions. PR= at least 30% decrease in sum of LDs of target lesion, taking as reference baseline sum LD. Stable/no response= neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LDs since treatment started. Objective progression= at least a 20% increase in sum of LDs of target lesions, taking as reference the smallest sum of LDs recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
  • Duration of Response (DR) [ Time Frame: Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks ]
    Time in weeks from first documentation of objective tumor response to objective tumor progression or symptomatic deterioration or death due to any cause, whichever occurred first. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or symptomatic deterioration or death due to any cause or last known progression-free date [if none of the event dates available] minus the date of the first CR or PR [which ever occurred first] that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
  • Overall Survival (OS) [ Time Frame: Baseline until end of treatment (15 August 2014); followed up every 8 weeks after discontinuation from study treatment. ]
    Time in weeks from randomization to date of death due to any cause. OS was calculated as (the death date or last known alive date (if death date unavailable) minus the date of randomization plus 1) divided by 7.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2008)
  • Trough concentrations of PF 00299804 after repeated dosing; [ Time Frame: 13months ]
  • Overall safety profile for patients in each arm [ Time Frame: 13 months ]
  • Patient Reported Outcomes (PRO) of health related quality of life and disease/treatment related symptoms for patients in each arm [ Time Frame: 13 months ]
  • KRAS and HER family mutations in circulating tumor DNA in blood and in tissue (from original diagnostic or recently obtained sample) [ Time Frame: 16 monhts ]
  • Best Overall Response per RECIST (BOR) for patients in each arm [ Time Frame: 10 months ]
  • Duration of Response for patients in each arm [ Time Frame: 13 months ]
  • Overall Survival for patients in each arm [ Time Frame: 16 months ]
  • Pre and post treatment levels of circulating shed receptors of the HER signaling pathways or protein/receptors which interact with or are part of HER signaling pathway [ Time Frame: 13 months ]
  • EGFR mutations, including T790M, in blood at baseline and at end of study [ Time Frame: 13 months ]
Current Other Pre-specified Outcome Measures
 (submitted: July 27, 2015)
  • Number of Participants With Kirsten Rat Sarcoma (KRAS) and Epidermal Growth Factor Receptor (EGFR) Status and EGFR T790M Mutation [ Time Frame: Baseline ]
    Tumor tissue were analyzed at a sponsor-designated laboratory to investigate KRAS and EGFR status (wild type or mutated). Participants who did not provide samples for central laboratory analysis confirmation were classified as "unknown". Additionally blood specimens were analyzed at a sponsor-designated laboratory for T790M mutation in EGFR.
  • Soluble Protein Biomarkers Level [ Time Frame: Cycle (C) 1 Day (D) 1 (baseline), D1 of each subsequent cycle up to end of treatment (up to 121 weeks) ]
    Blood specimens were analyzed at a sponsor-designated laboratory for analysis of shed proteins/receptors related to Human Epidermal Growth Factor Receptor (HER) signaling (EGFR, HER-2, Epithelial-cadherin [E-cadherin]). The data collection after C12D1 was not performed, as there were too few participants across both treatment arms after C12D1.
  • Trough Plasma Concentration (Ctrough) of Dacomitinib (PF-00299804) [ Time Frame: C1D10-14, C2D1, C3D1, C4D1 ]
    Only participants from "Dacomitinib" treatment arm were planned to be analyzed for this outcome.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Randomized Trial Of PF-00299804 Taken Orally Versus Erlotinib Taken Orally For Treatment Of Advanced Non-Small Cell Lung Cancer That Has Progressed After One Or Two Prior Chemotherapy Regimen
Official Title  ICMJE A Randomized Phase 2 Trial Of Pf-00299804 Versus Erlotinib For The Treatment Of Advanced Non-small Cell Lung Cancer After Failure Of At Least One Prior Chemotherapy Regimen
Brief Summary This study will compare PF-00299804 given orally on continuous schedule to the approved drug, erlotinib, in patients whose non-small cell lung cancer has progressed after chemotherapy; patients will be randomized to receive one of these drugs, and followed for efficacy and tolerance of each.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Erlotinib
    Continuous oral dosing at 150 mg daily.
  • Drug: PF-00299804
    Continuous oral dosing at 45mg daily
Study Arms  ICMJE
  • Active Comparator: A
    Intervention: Drug: Erlotinib
  • Experimental: B
    Intervention: Drug: PF-00299804
Publications * Ramalingam SS, O'Byrne K, Boyer M, Mok T, Jänne PA, Zhang H, Liang J, Taylor I, Sbar EI, Paz-Ares L. Dacomitinib versus erlotinib in patients with EGFR-mutated advanced nonsmall-cell lung cancer (NSCLC): pooled subset analyses from two randomized trials. Ann Oncol. 2016 Mar;27(3):423-9. doi: 10.1093/annonc/mdv593. Epub 2016 Jan 13. Erratum in: Ann Oncol. 2016 Jul;27(7):1363.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 18, 2011)
188
Original Estimated Enrollment  ICMJE
 (submitted: October 7, 2008)
160
Actual Study Completion Date  ICMJE August 2014
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • advanced measurable Non-Small Cell Lung Cancer (NSCLC);
  • progressed after 1-2 prior chemotherapy;
  • Eastern Cooperative Oncology Group (ECOG) 0-2;
  • tissue available for future KRAS/ EGFR testing

Exclusion Criteria:

  • prior Epidermal Growth Factor Receptor (EGFR) targeted therapy;
  • active or untreated Central Nervous System (CNS) metastases;
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Brazil,   Canada,   Hong Kong,   Korea, Republic of,   Poland,   Puerto Rico,   Singapore,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00769067
Other Study ID Numbers  ICMJE A7471028
2008-005235-14 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date September 2015

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