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

• ClinicalTrials.gov Identifier: NCT00932451
• Recruitment Status: Completed
• First Posted: July 3, 2009
• Results First Posted: June 9, 2016
• Last Update Posted: January 13, 2017
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: June 30, 2009
• First Posted Date: July 3, 2009
• Results First Submitted Date: March 14, 2016
• Results First Posted Date: June 9, 2016
• Last Update Posted Date: January 13, 2017
• Study Start Date: January 2010
• Actual Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 17, 2016)

• Objective Response Rate [ Time Frame: 6 years ]
  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: 6 years ]
  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).

• Original Primary Outcome Measures (submitted: July 2, 2009): Objective Response Rate [ Time Frame: 30 months ]

Current Secondary Outcome Measures (submitted: November 17, 2016)

• Duration of Response (DR) [ Time Frame: 6 years ]
  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: 6 years ]
  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: 6 years ]
  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: 6 years ]
  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.
• Overall Survival (OS) [ Time Frame: 6 years ]
  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: 6 years ]
  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.
• Plasma Concentrations of Crizotinib (PF-02341066) and Its Metabolite PF-06260182 [ Time Frame: 6 years ]
  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: 6 years ]
  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: 6 years ]
  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: 6 years ]
  The percentage of participants with maximum post-dose QTcF/QTcB (<450, 450 - <480, 480 - <500, and ≥500 msec) were evaluated.
• Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. [ Time Frame: 6 years ]
  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.
• Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores [ Time Frame: 6 years ]
  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: 6 years ]
  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.
• Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) [ Time Frame: 6 years ]
  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.
• 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: 6 years ]
  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.

Original Secondary Outcome Measures (submitted: July 2, 2009)

• Duration of Response [ Time Frame: 30 months ]
• Disease Control Rate [ Time Frame: 30 months ]
• Overall Survival [ Time Frame: 30 months ]
• Patient reported symptoms of lung cancer and health-related quality of life [ Time Frame: 30 months ]
• Type, incidence, severity, seriousness and relationship to study medication of adverse events and laboratory test abnormalities [ Time Frame: 30 months ]
• Plasma concentrations of PF-02341066 [ Time Frame: 30 months ]
• Types of EML4-ALK fusion variants and ALK gene expression [ Time Frame: 30 months ]
• Protein expression of identified biomarkers in serial tumor samples (when available) [ Time Frame: 30 months ]
• Progression Free Survival [ Time Frame: 30 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Non-Small-Cell Lung

Intervention

Drug: PF-02341066

PF-02341066, 250 mg BID, will be administered orally on a continuous schedule

Study Arms

Experimental: PF-0231066

Intervention: Drug: PF-02341066

Publications *

• Camidge DR, Kim EE, Usari T, Polli A, Lewis I, Wilner KD. Renal Effects of Crizotinib in Patients With ALK-Positive Advanced NSCLC. J Thorac Oncol. 2019 Jun;14(6):1077-1085. doi: 10.1016/j.jtho.2019.02.015. Epub 2019 Feb 26.
• Blackhall F, Ross Camidge D, Shaw AT, Soria JC, Solomon BJ, Mok T, Hirsh V, Janne PA, Shi Y, Yang PC, Pas T, Hida T, Carpeno JC, Lanzalone S, Polli A, Iyer S, Reisman A, Wilner KD, Kim DW. Final results of the large-scale multinational trial PROFILE 1005: efficacy and safety of crizotinib in previously treated patients with advanced/metastatic ALK-positive non-small-cell lung cancer. ESMO Open. 2017 Aug 17;2(3):e000219. doi: 10.1136/esmoopen-2017-000219. eCollection 2017.
• Yoneda KY, Scranton JR, Cadogan MA, Tassell V, Nadanaciva S, Wilner KD, Stollenwerk NS. Interstitial Lung Disease Associated With Crizotinib in Patients With Advanced Non-Small Cell Lung Cancer: Independent Review of Four PROFILE Trials. Clin Lung Cancer. 2017 Sep;18(5):472-479. doi: 10.1016/j.cllc.2017.03.004. Epub 2017 Mar 14.
• Lin YT, Yu CJ, Yang JC, Shih JY. Anaplastic Lymphoma Kinase (ALK) Kinase Domain Mutation Following ALK Inhibitor(s) Failure in Advanced ALK Positive Non-Small-Cell Lung Cancer: Analysis and Literature Review. Clin Lung Cancer. 2016 Sep;17(5):e77-e94. doi: 10.1016/j.cllc.2016.03.005. Epub 2016 Mar 30.
• Costa DB, Shaw AT, Ou SH, Solomon BJ, Riely GJ, Ahn MJ, Zhou C, Shreeve SM, Selaru P, Polli A, Schnell P, Wilner KD, Wiltshire R, Camidge DR, Crino L. Clinical Experience With Crizotinib in Patients With Advanced ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastases. J Clin Oncol. 2015 Jun 10;33(17):1881-8. doi: 10.1200/JCO.2014.59.0539. Epub 2015 Jan 26.
• Lin YT, Wang YF, Yang JC, Yu CJ, Wu SG, Shih JY, Yang PC. Development of renal cysts after crizotinib treatment in advanced ALK-positive non-small-cell lung cancer. J Thorac Oncol. 2014 Nov;9(11):1720-5. doi: 10.1097/JTO.0000000000000326.
• Ou SH. Crizotinib: a drug that crystallizes a unique molecular subset of non-small-cell lung cancer. Expert Rev Anticancer Ther. 2012 Feb;12(2):151-62. doi: 10.1586/era.11.186.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 17, 2016): 1069
• Original Estimated Enrollment (submitted: July 2, 2009): 200
• Actual Study Completion Date: December 2015
• Actual Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Brazil, Bulgaria, Canada, China, France, Germany, Greece, Hong Kong, Hungary, Ireland, Italy, Japan, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, Sweden, Taiwan, United Kingdom, United States
• Removed Location Countries: Argentina

Administrative Information

• NCT Number: NCT00932451
• Other Study ID Numbers: A8081005; 2009-012504-13 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: November 2016