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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: PF-02341066


Participation Criteria
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Eligibility Criteria
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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

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: PF-0231066<br> | Drug: PF-02341066<br>* PF-02341066, 250 mg BID, will be administered orally on a continuous schedule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | 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. | 6 years | 
| Percentage of Participants With Adverse Events | 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). | 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DR) | 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. | 6 years | 
| Time to Tumor Response (TTR) | 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. | 6 years | 
| Disease Control Rate (DCR) | 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. | 6 years | 
| Progression Free Survival (PFS) | 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. | 6 years | 
| Overall Survival (OS) | 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. | 6 years | 
| Probability of Survival | 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. | 6 years | 
| Plasma Concentrations of Crizotinib (PF-02341066) and Its Metabolite PF-06260182 | Plasma concentrations of crizotinib (PF-02341066) and its metabolite PF-06260182. The method of dispersion is % coefficient of variation. | 6 years | 
| Molecular Profiling (ALK Status) Descriptive Statistics for ALK Percentage of Positive Cells by Central Laboratory Test (SA [ALK Positive by IUO] Population) | 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. | 6 years | 
| Genotypes of Alleles Possibly Associated With Adverse Hepatic Drug Reactions (Pharmacogenomic Evaluable Population) | 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. | 6 years | 
| QTc Prolongation in Participants | The percentage of participants with maximum post-dose QTcF/QTcB (<450, 450 - <480, 480 - <500, and ≥500 msec) were evaluated. | 6 years | 
| Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. | 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. | 6 years | 
| Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores | 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. | 6 years | 
| Mean Change From Baseline of QLQ-LC13 Scale Scores | 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. | 6 years | 
| Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) | 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. | 6 years | 
| Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale | 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. | 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Neoplasms ALK gene Crizotinib