NCT02923947

Study to Assess Osimertinib in Patients w/ Adv Solid Tumours & Normal Kidney Function or Severe Kidney Impairment

Open-label,Non-randomised,Multicentre,Phase I Study to Assess the Pharmacokinetics, Safety & Tolerability of Osimertinib Following a Single Oral 80mg Dose to Patients w/ Adv Solid Tumours & Normal Renal Function or Severe Renal Impairment.

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 130 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Solid Tumours

Interventions

Type	Name	Description
DRUG	Osimertinib; AZD9291	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

Timeline

• Start date: 2017-05-04
• Primary completion: 2018-09-20
• Completion: 2022-10-28
• First posted: 2016-10-05
• Last updated: 2023-11-27

Locations

11 sites across 3 countries: France, South Korea, Spain