A Study Of Crizotinib Versus Chemotherapy In Previously Untreated ALK Positive East Asian Non-Small Cell Lung Cancer Patients
Condition: NSCLC (Non-small Cell Lung Cancer)
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Crizotinib; Pemetrexed/Cisplatin; Pemetrexed/Carboplatin
Intervention description: 250 mg two times daily [BID], oral, on a continuous daily dosing schedule. Cycles are defined in 21 day periods.; Option 1: Pemetrexed/Cisplatin; Pemetrexed, 500 mg/m^2, will be administered by intravenous infusion over 10 minutes or according to institutional administration timing on Day 1 of a 21-day cycle. Cisplatin, 75 mg/m^2 will be administered by infusion after adequate hydration according to institutional practices beginning approximately 30 minutes after the end of the pemetrexed infusion. Pemetrexed and cisplatin will be repeated every 3 weeks for a maximum of 6 cycles.; Option 2: Pemetrexed/Carboplatin. Pemetrexed, 500 mg/m^2, will be administered by intravenous infusion over 10 minutes or according to institutional administration timing on Day 1 of a 21-day cycle. Carboplatin, at a dose calculated to produce an AUC of 5 or 6 mg.min/mL will be administered by infusion according to institutional practices beginning approximately 30 minutes after the end of the pemetrexed infusion. Pemetrexed and carboplatin will be repeated every 3 weeks for a maximum of 6 cycles.
Intervention MeSH terms: Carboplatin; Pemetrexed; Crizotinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 207.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Crizotinib; ALK positive; ALK; Anaplastic Lymphoma Kinase; NSCLC; Non-Small Cell Lung Cancer; Frontline; 1L; Previously Untreated; East Asian; Non-Squamous

Summary:

      This is a Phase III, Randomized, Open-label, Efficacy and Safety Study of Crizotinib single
      agent versus Chemotherapy Regimens (Pemetrexed/Cisplatin or Pemetrexed/Carboplatin) in
      First-Line ALK (Anaplastic Lymphoma Kinase) Positive East Asian Non-Small Cell Lung Cancer
      Patients. The objective of the study is to demonstrate that Crizotinib is superior to
      first-line chemotherapy pemetrexed/cisplatin or pemetrexed/carboplatin in prolonging
      Progression Free Survival (PFS) in East Asian patients with advanced Non-Squamous NSCLC whose
      tumors harbor a translocation or inversion event involving the ALK (Anaplastic Lymphoma
      Kinase) gene locus.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically proven diagnosis of locally advanced not suitable for
             local treatment, recurrent and metastatic non-squamous cell carcinoma of the lung.

          -  Positive for translocation or inversion events involving the ALK gene locus.

          -  No prior systemic treatment for locally advanced or metastatic disease. Patients with
             brain metastases only if treated and neurologically stable for at least 2 weeks and
             are not taking any medications contraindicated in Exclusion Criteria

          -  Evidence of a personally signed and dated informed consent document and willingness
             and ability to comply with scheduled visits, treatment plans, laboratory tests, and
             other study procedures including completion of patient reported outcome [PRO]
             measures.

        Exclusion Criteria:

          -  Current treatment on another therapeutic clinical trial.

          -  Prior therapy directly targeting ALK.

          -  Any of the following within the 3 months prior to starting study treatment: myocardial
             infarction, severe/unstable angina, coronary/peripheral artery bypass graft,
             congestive heart failure, or cerebrovascular accident including transient ischemic
             attack. Appropriate treatment with anticoagulants is permitted.

          -  Ongoing cardiac dysrhythmias of NCI CTCAE Grade >=2, uncontrolled atrial fibrillation
             of any grade, or QTc interval >470 msec.

          -  Pregnancy or breastfeeding.

          -  Use of drugs or foods that are known potent CYP3A inducers/inhibitors Concurrent use
             of drugs that are CYP3A substrates with narrow therapeutic indices.

          -  Known HIV infection

          -  History of extensive disseminated/bilateral or known presence of Grade 3 or 4
             interstitial fibrosis or interstitial lung disease, including a history of
             pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung
             disease, obliterative bronchiolitis, and pulmonary fibrosis, but not history of prior
             radiation pneumonitis.

          -  Other severe acute or chronic medical conditions (including severe gastrointestinal
             conditions such as diarrhea or ulcer) or psychiatric conditions, or end-stage renal
             disease on hemodialysis, or laboratory abnormalities that would impart, in the
             judgment of the investigator and/or sponsor, excess risk associated with study
             participation or study drug administration, and which would, therefore, make the
             patient inappropriate for entry into this study.