Phase I, Study in Chinese NSCLC Patients
Condition: Carcinoma, Non-Small-Cell Lung With EGFR Mutation Positive
MeSH terms: Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 1

Summary: 
      A Phase I, Open-Label, Two Parts Study to Assess the Safety, Tolerability,Pharmacokinetics
      and Preliminary Anti-tumour Activity of AZD9291 in Chinese Patients with Advanced Non-Small
      Cell Lung Cancer who have Progressed Following Prior Therapy with an Epidermal Growth Factor
      Receptor Tyrosine Kinase Inhibitor Agent

      Study Objective: 1, Primary Objective To characterise the pharmacokinetics (PK) of AZD9291
      and its metabolites (AZ5104 and AZ7550) after single then multiple doses of AZD9291
      administered orally once daily in Chinese patients with locally advanced or metastatic non
      small cell lung Cancer (NSCLC) who have progressed following prior therapy with an approved
      Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) agent.

      2, Secondary objective(s) To investigate the safety and tolerability of AZD9291 when given
      orally to Chinese patients with locally advanced or metastatic NSCLC who have progressed
      following prior therapy with an approved EGFR TKI agent. To obtain a preliminary assessment
      of the anti-tumour activity of AZD9291 by evaluation of tumour response using Response
      Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
    

Detailed description: 
      This is a phase I, open-label, two parts (Part A and Part B) study to determine the
      pharmacokinetics of AZD9291 administered orally at two dose levels (40 mg and 80 mg) in
      patients with locally advanced or metastatic NSCLC who have progressed following prior
      therapy with an approved EGFR TKI agent (+/- additional chemotherapy regimens).

      Approximately 24 patients will enter into this study, with 12 patients at each dose level.

        -  Cohort 1 will investigate the pharmacokinetics of single then multiple dosing of AZD9291
           at 40 mg once daily dose.

        -  Cohort 2 will investigate the pharmacokinetics of single then multiple dosing of AZD9291
           at 80 mg once daily dose.

      The enrollment of Cohort 2 will start after Cohort 1 finishes the enrollment. The first 12
      patients enrolled in the study will be in 40 mg dose Cohort.

      Patients will be administered a single dose of AZD9291 on Day 1, Cycle 0 at the beginning of
      Part A period. From Day 2 to Day 6, no treatment will be given, but PK samples will be
      obtained; on Day 7 (Cycle1, Day1), the patients will be administered AZD9291 once daily on a
      continuous schedule, ie, no break in AZD9291 dosing. Part A will complete after Cycle 4
      treatment and Part B will start without treatment interruption.

      Patients in both cohorts should continue on treatment with AZD9291 until a treatment
      discontinuation criterion is met. There is no maximum duration of treatment as patients may
      continue to receive AZD9291 beyond RECIST 1.1 defined progression as long as they are
      continuing to receive clinical benefit, as judged by the investigator.

      The whole study will be divided nominally into two parts: Part A will assess the
      pharmacokinetics and preliminary efficacy and safety of AZD9291 at 40 mg and 80 mg
      respectively, and Part B will assess only the safety and efficacy data of AZD9291.

      Following completion of the Part A, patients will automatically continue to Part B.
    

Intervention name(s): AZD9291 40 mg; AZD9291 80 mg
Intervention type(s): Drug; Drug
Intervention description(s): This is a two parts (Part A and Part B) study to determine the pharmacokinetics of AZD9291 administered orally at two dose levels (40 mg Cohort 1 and 80 mg Cohort 2) in patients with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens).; This is a two parts (Part A and Part B) study to determine the pharmacokinetics of AZD9291 administered orally at two dose levels (40 mg Cohort 1 and 80 mg Cohort 2) in patients with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens).
Intervention MeSH terms: Osimertinib
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other