An Investigational Drug, PF-02341066, Is Being Studied In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00932451
First received: June 30, 2009
Last updated: April 28, 2016
Last verified: April 2016
  Purpose
This is a Phase 2 trial that will evaluate the safety and efficacy of PF-02341066 in patients with advanced non-small cell lung cancer with a specific gene profile involving the ALK gene. This trial will also allow patients from a Phase 3 trial who received standard of care chemotherapy (Study A8081007) to receive PF-02341066.

Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: PF-02341066
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2, Open-Label Single Arm Study Of The Efficacy And Safety Of PF-02341066 In Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Harboring A Translocation Or Inversion Involving The Anaplastic Lymphoma Kinase (ALK) Gene Locus

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Objective Response Rate [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    The objective response rate (ORR) as a measure of anti-tumor efficacy of oral PF-02341066 in participants with advanced NSCLC with an ALK gene translocation or inversion after failure of at least one line of chemotherapy.

  • Percentage of Participants With Adverse Events [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    Incidence of adverse events and laboratory abnormalities (severity graded by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 4.0).


Secondary Outcome Measures:
  • Duration of Response (DR) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    DR was defined as the time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed, to the first documentation of objective tumor progression or to death on study due to any cause, whichever occurred first. DR (in months) was calculated as (first date of PD or death − first date of CR or PR that was subsequently confirmed + 1)/30.4.

  • Time to Tumor Response (TTR) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    TTR was defined as the time (in weeks) from the date of Cycle 1 Day 1 dose to first documentation of objective tumor response (CR or PR) that was subsequently confirmed. For participants proceeding from PR to CR, the onset of PR was taken as the onset of response.

  • Disease Control Rate (DCR) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    DCR at 6 and 12 weeks was defined as the percentage of participants with a confirmed CR, confirmed PR, or SD (according to RECIST v 1.1) at 6 weeks and 12 weeks, respectively.

  • Progression Free Survival (PFS) [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    PFS was defined as the time from the date of the Cycle 1 Day 1 dose to the date of the first documentation of objective tumor progression or death on study due to any cause, whichever occurred first.

  • Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    The EORTC QLQ-C30 consists of 30 questions which assess five functional domains (physical, role, cognitive, emotional, and social), global health status/quality of life, disease/treatment related symptoms (fatigue, pain, nausea/vomiting, dyspnea, appetite loss, sleep disturbance, constipation, and diarrhoea), and the perceived financial impact of disease. n is the number of participants who completed the scale at baseline and at the respective Cycle. The subscales of the EORTC QLQ-C30 were scored based on the EORTC scoring manual. The transformed scores range from 0-100. Higher scores indicate higher ("worse") symptom severity, higher ("better") functioning, and better global QoL. Negative change from Baseline scores indicate an improvement in symptoms, decreased functioning, or decreased QoL, while positive change scores indicate an increase in functioning, increased QoL, or deterioration in symptoms.

  • Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    The EQ-5D descriptive system measured a patient's health state on 5 dimensions which included: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The respondent's self-rated health was assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) by the EQ-VAS. n is the number of participants who completed the scale at baseline and at the respective Cycle.

  • Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    The participants who responded to the question: "Have you experienced any visual disturbances?" Only the participants who answered yes were instructed to complete the rest of the questionnaire. N was the number of participants who had completed the first question.

  • Plasma Concentrations of Crizotinib (PF-02341066) and Its Metabolite PF-06260182 [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Plasma concentrations of crizotinib (PF-02341066) and its metabolite PF-06260182. The method of dispersion is % coefficient of variation.

  • Molecular Profiling (ALK Status) Descriptive Statistics for ALK Percentage of Positive Cells by Central Laboratory Test (SA [ALK Positive by IUO] Population) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Molecular profiling outcomes included:Types of EML4-ALK fusion variants and ALK protein expression; Although a secondary objective was defined to explore the relationship of ALK gene fusion to the presence of ALK protein and fusion transcript, no additional analyses of ALK fusion variants or ALK protein were performed for technical reasons. Analyses of change from Baseline in the expression of biomarkers relevant to signaling pathways were not performed because paired Baseline and on-treatment (Cycle 2) tumor tissue required for the analysis, which were to be collected on an optional basis, were not available.

  • Genotypes of Alleles Possibly Associated With Adverse Hepatic Drug Reactions (Pharmacogenomic Evaluable Population) [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    The frequency of the candidate gene alleles, HLA-DQA1*02:01, HLA-DQB1*02:02, HLA-DRB1*07:01 and TNXB/rs12153855, were measured in alanine transaminase (ALT) Cases and ALT Controls to evaluate if there were statistically significant associations that would support or suggest any predictive (ie, diagnostic) value of these markers in identifying participants who were at increased risk for hepatic toxicity. The frequency of 2 additional HLA gene alleles, HLA-B*57:01 and HLA-DRB1*15:01, were also measured in ALT Cases and ALT Controls. ALT Cases are defined as those patients with a baseline ALT of ≤1xULN and at least one on-treatment ALT assessment of >3x upper limit of normal (ULN), and ALT Controls represent those patients with baseline and on-treatment assessments of ALT of ≤1xULN.

  • QTc Prolongation in Participants [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    The percentage of participants with maximum post-dose QTcF/QTcB (<450, 450 - <480, 480 - <500, and ≥500 msec) were evaluated.

  • Overall Survival (OS) [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    OS was defined as the time from the Cycle 1 Day 1 dose to the date of death due to any cause. OS (in months) was calculated as (date of death − date of Cycle 1 Day 1 dose + 1)/30.4.

  • Probability of Survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    Six-month and 1-year survival probabilities were defined as the probabilities of survival at 6 months and 1 year, respectively, after the date of the Cycle 1 Day 1 dose based on the Kaplan-Meier estimate.

  • Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    The EORTC QLQ-C30 consists of 30 questions which assess five functional domains (physical, role, cognitive, emotional, and social), global health status/quality of life, disease/treatment related symptoms (fatigue, pain, nausea/vomiting, dyspnoea, appetite loss, sleep disturbance, constipation, and diarrhoea), and the perceived financial impact of disease. n is the number of participants who completed the scale at baseline and at the respective Cycle. The subscales of the EORTC QLQ-C30 were scored based on the EORTC scoring manual. The transformed scores range from 0-100. Higher scores indicate higher ("worse") symptom severity, higher ("better") functioning, and better global QoL. Negative change from Baseline scores indicate an improvement in symptoms, decreased functioning, or decreased QoL, while positive change scores indicate an increase in functioning, increased QoL, or deterioration in symptoms.

  • Mean Change From Baseline of QLQ-LC13 Scale Scores [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    The QLQ-LC13 consists of 1 multi-item scale and 9 single items that assess specific symptoms (dyspnoea, cough, hemoptysis, and site-specific pain), side effects (sore mouth, dysphagia, neuropathy, and alopecia), and pain medication use of lung cancer patients. n is the number of participants who completed the scale at baseline and at the respective Cycle. The subscales of the EORTC QLQ-LC13 were scored based on the EORTC scoring manual. The transformed scores range from 0-100. Higher scores indicate higher ("worse") symptom severity, higher ("better") functioning, and better global QoL. Negative change from Baseline scores indicate an improvement in symptoms, decreased functioning, or decreased QoL, while positive change scores indicate an increase in functioning, increased QoL, or deterioration in symptoms.


Enrollment: 1068
Study Start Date: January 2010
Study Completion Date: December 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PF-0231066 Drug: PF-02341066
PF-02341066, 250 mg BID, will be administered orally on a continuous schedule

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • histologically or cytologically proven diagnosis of non-small cell lung cancer
  • positive for the ALK fusion gene (test provided by either a central laboratory. Local laboratory may be used for certain cases)
  • may have received pemetrexed or docetaxel from previous Phase 3 trial (A8081007) and discontinued treatment due to Response Evaluation Criterion in Solid Tumors (RECIST)-defined progression. or, once the primary endpoint of Study A8081007 has been analyzed and the results made available, at any time without RECIST-defined progression.
  • Tumors can be measurable or non measurable

Exclusion Criteria:

  • prior treatment with PF-02341066
  • received no prior systemic treatment, chemotherapy or EGFR tyrosine kinase inhibitor, for advanced non-small cell lung cancer
  • current enrollment in another therapeutic clinical trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00932451

  Show 279 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00932451     History of Changes
Other Study ID Numbers: A8081005  2009-012504-13 
Study First Received: June 30, 2009
Results First Received: March 14, 2016
Last Updated: April 28, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Lung Neoplasms ALK gene Crizotinib

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Crizotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 23, 2016