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
Primary Objectives: 1. To assess the anti-tumor efficacy of oral single agent PF-02341066 administered to patients with advanced NSCLC after failure of at least one line of chemotherapy and harbor a translocation or inversion event involving the ALK gene locus as measured by objective response rate (ORR) 2. To assess the safety and tolerability of oral PF-02341066 Secondary Objectives: 1. To assess secondary measures of clinical efficacy including overall survival (OS), duration of response (DR), disease control rate (DCR) at 6 and 12 weeks, and progression-free survival (PFS) 2. To determine PK in this patient population using population PK (POPPK) methods and explore correlations between PK, response and/or safety findings 3. To explore the relationship of ALK gene fusion to the presence of ALK protein and fusion transcript 4. To correlate changes from baseline in expression of biomarkers in signaling pathways (including JAK/STAT, MEK/ERK, and PI3K/AKT pathways) to pharmacokinetic and outcome measures 5. To assess patient reported outcomes(PRO) of health-related quality of life (HRQoL), disease/treatment-related symptoms of lung cancer, and general health status Endpoints: Primary Endpoints: 1. ORR 2. Type, incidence, severity, seriousness and relationship to study medications of adverse events (AE) and any laboratory abnormalities Secondary Endpoints: 3. OS, DR, DCR at 6 and 12 weeks, and PFS 4. Plasma concentrations of PF-02341066 5. Types of EML4-ALK fusion variants and ALK protein expression 6. Protein expression of identified biomarkers in serial tumor samples from surgery or biopsy, when available 6. HRQoL, lung cancer specific symptoms, and general health status
1. Histologically or cytologically proven diagnosis of NSCLC that is locally advanced or Metastatic 2. Positive for translocation or inversion events involving the ALK gene locus (e.g. resulting in EML4-ALK fusion) as determined by an ALK break apart FISH assay and defined by an increase in the distance of 5ï¿½ and 3ï¿½ ALK probes or the loss of the 5ï¿½ probe 3. Meets one of the following criteria: 1. Randomized to Arm B (pemetrexed or docetaxel) of Study A8081007 and was discontinued from treatment due to RECIST version 1.1-defined progression of disease as determined by independent radiology review 2. Ineligibility for A8081007 due to (1) prior treatment for advanced disease with more than one chemotherapy regimen, (2) prior treatment with only one chemotherapy regimen for advanced disease and that regimen was not platinum-based, (3) prior treatment with pemetrexed as part of their platinum-based chemotherapy and did not meet the docetaxel eligibility requirements from Protocol A8081007 or (4) treated with docetaxel as part of their platinum-based prior chemotherapy but have NSCLC that is predominantly squamous cell carcinoma and thus, not eligible to be dosed with pemetrexed.
This is an open-label, multi-center, single arm Phase 2 trial of an oral agent, PF-02341066, in patients with advanced NSCLC harboring a translocation or inversion event involving the ALK gene locus. Only ALK fusion positive patients may enter the study. Approximately 100 patients are expected to cross over upon progression from Study A8081007. Additionally, up to 150 patients are expected to be enrolled from different sources. Thus, a total of 250 patients are expected to be enrolled into this trial. ALK break apart fluorescence in situ hybridization (FISH) assay will be used as the primary assay for detecting ALK fusion events in tumor samples for determining the eligibility of patients for entering the trial. For patients that have already provided a tissue sample for testing for Study A8081007, an additional FISH analysis is not required. For new patients, clinical sites will be required to send the tumor samples (tumor block or slides) to the central laboratory, selected by the Sponsor, for analysis. Patients may continue treatment with PF-02341066 on this trial as long as there is evidence of clinical benefit in the judgment of the investigator. PF-02341066, 250 mg BID, will be administered orally at approximately the same time each day on a continuous daily dosing schedule, i.e. no break in dosing. PF-02341066 can be dosed without regard to meals. Cycles are defined in 21-day periods to facilitate scheduling of visits and assessments.
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