Study to Assess Osimertinib in Patients w/ Adv Solid Tumours & Normal Kidney Function or Severe Kidney Impairment
Condition: Solid Tumours
MeSH terms: Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to assess the effect of severe renal impairment on the levels of
      AZD9291 in the blood in patients with advanced solid tumours compared to patients with normal
      renal function
    

Detailed description: 
      This is a 3-part study (Part A, Part B and continued access) in patients with advanced solid
      tumours (excluding lymphoma) that are refractory to standard therapies or for which no
      standard therapies exist.

      Part A will have a non-randomised, open-label, parallel group, multi-centre design to
      investigate the pharmacokinetics (PK) of a single dose of osimertinib in patients with severe
      renal impairment compared with patients with normal renal function. Patients with severe
      renal impairment will be recruited before those with normal renal function to allow the
      cohorts to be matched as closely as possible in terms of demographic characteristics (ie,
      age, body mass index [BMI] and sex).

      Approximately 16 patients (8 with severe renal impairment and 8 with normal renal function)
      are planned to be enrolled to obtain at least 12 evaluable patients (6 with severe renal
      impairment and 6 with normal renal function) in Part A. A patient with severe renal
      impairment (as measured by the Cockcroft-Gault equation) is defined as having a creatinine
      clearance (CrCl) of <30 mL/min whilst a patient with normal renal function has a CrCl of ≥90
      mL/min. Both the severe renal impairment and normal renal function patients will be recruited
      such that both groups will be matched for age, sex, and BMI to the maximum extent possible.

      In Part A, each patient will receive a single oral dose of osimertinib 80 mg (given as a
      tablet). Where possible, patients will check into the clinic on Day -1, the evening prior to
      dosing (Day 1), and remain resident until 24 hours after the dose of osimertinib (Day 2) for
      collection of blood samples and 24-hour pooled urine for PK analysis during this time.
      Samples will be analysed to determine the concentrations of osimertinib and metabolites
      (AZ5104 and AZ7550) in plasma, urine, and plasma ultrafiltrate (PUF). Patients will then
      return to the clinic as outpatients for assessments on Day 3 (48 hours), Day 4 (72 hours),
      Day 6 (120 hours), Day 8 (168 hours) and Day 10 (216 hours).

      Part B will allow patients with severe renal impairment, who complete Part A, to continue to
      receive osimertinib 80 mg once daily for 12 weeks and will provide additional safety data.
      Patients should start Part B after the last PK sample collected in Part A (ie, 216 hours
      after receiving the single dose of osimertinib in Part A).

      If a patient does not immediately continue into Part B, this should be discussed on a case by
      case basis with the AstraZeneca physician or representative. Patients who enter Part B, will
      have weekly clinic visits for the first 3 weeks; thereafter visits will be every 3 weeks
      until Week 12. Safety assessments will be collected and there will be no formal evaluation of
      efficacy.

      At the end of Part B, those patients with severe renal impairment who are deemed to be
      gaining clinical benefit from osimertinib will enter the continued access phase. Patients
      with normal renal function can enter the continued access phase immediately after completing
      Part A (ie, collection of the last PK sample scheduled on Day 10 of Part A). During the
      continued access phase, patients may continue to take osimertinib 80 mg once daily, if
      patients and the Investigator deem it appropriate, or until such time as their disease
      progresses, the Investigator believes the patients are no longer deriving clinical benefit,
      or patients stop taking osimertinib for any other reason. No clinical data, other than
      serious adverse events (SAEs) that may be related to the investigational product (IP), will
      be collected during this phase.
    

Intervention name(s): Osimertinib; AZD9291
Intervention type(s): Drug
Intervention description(s): 80mg tablet dose to be taken orally - single dose in part A, daily dosing in Part B and continued access until progression or no longer receiving benefit
Other intervention name(s): TAGRISSO™
Intervention MeSH terms: Osimertinib
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Pharmacokinetics,; Renal impairment,; Safety assessments,; Solid tumours,; EGFRm+; EGFRm+/T790M+ inhibitor