AZD9291 (Osimertinib) Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Condition: Anticancer Treatment
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Chemotherapy; Cross-over to Osimertinib
Intervention description: Randomization to either Osimertinib or platinum-based doublet-chemotherapy on Day 1 of every 21d cycle in a 2:1 (Osimertinib:platinum-based doublet-chemotherapy) ratio; Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by independent central imaging review, they will be given the opportunity to begin treatment with Osimertinib 80mg, once daily. These subjects may continue treatment with Osimertinib even after disease progression, as long as they are continuing to show clinical benefit, as judged by the investigator.
Subjects who stop platinum-based doublet chemotherapy for reasons other than objective disease progression according to RECIST 1.1 will not be eligible to cross-over to Osimertinib.
Intervention MeSH terms: Osimertinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 419.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Advanced Non-Small Cell Lung Cancer; T790M Mutation Positive

Summary:

      A Phase III, Open Label, Randomized Study of Osimertinib versus Platinum-Based Doublet
      Chemotherapy for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer
      whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase
      Inhibitor Therapy and whose Tumours harbour a T790M mutation within the Epidermal Growth
      Factor Receptor Gene
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects with histologically or cytologically documented NSCLC.

          -  Locally advanced or metastatic NSCLC

          -  Radiological documentation of disease progression following 1st line EGFR TKI
             Treatment without any further treatment

          -  Eligible to receive treatment with the selected doublet-chemotherapy

          -  Central confirmation of T790M+ mutation status

          -  World Health Organization (WHO) performance status 0-1

          -  At least one lesion, not previously irradiated.

        Exclusion Criteria:

          -  • Prior neo-adjuvant or adjuvant chemotherapy treatment within 6 months prior of
             starting 1st EGFR TKI treatment

          -  Treatment with more than one prior line of treatment for advanced NSCLC

          -  Treatment with an approved EGFR-TKI (e.g.,erlotinib, gefitinib, afatinib) within 8
             days or approximately 5x half-life of the first dose of study treatment

          -  Any investigational agents or other anticancer drugs from a previous treatment regimen
             or clinical study within 14 days of the first dose of study treatment

          -  Previous treatment with Osimertinib, or a 3rd generation EGFR TKI

        For subjects who cross-over to Osimertinib:

          -  Once subjects on the platinum-based doublet chemotherapy arm are determined to have
             objective radiological progression according to RECIST 1.1 by the investigator and
             confirmed by independent central imaging review.

          -  At least 14 days since last dose of platinum-based doublet chemotherapy