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

NCT02923947 | Completed Phase 1

• 1 other identifier: D5160C00035
• Study Type: interventional
• Target: 16
• Locations: 3 countries
• Sites: 11

Brief 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

Conditions

Solid Tumours

Keywords

Pharmacokinetics,; Renal impairment,; Safety assessments,; Solid tumours,; EGFRm+; EGFRm+/T790M+ inhibitor

Outcome Measures

Primary Outcomes (2)

• Area under the plasma concentration-time curve from zero to infinity for osimertinib

  Part A: To investigate the PK of osimertinib after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.

  On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs post-dose

• Maximum plasma concentration for osimertinib

  Part A: To investigate the PK of osimertinib after a single oral dose of 80 mg in patients with advanced solid tumours and normal renal function or severe renal impairment.

  On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs post-dose

Secondary Outcomes (38)

• Area under the plasma concentration-time curve from zero to the last quantifiable time point for osimertinib

  On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose

• Area under the plasma concentration-time curve from zero to 24 hours post-dose for osimertinib

  On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24hrs for osimertinib post-dose

• Time to maximum plasma concentration for osimertinib

  On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose

• Apparent clearance following oral administration for osimertinib

  On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose

• Apparent volume of distribution for osimertinib

  On Day of dosing in Part A - predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, 120, 168, 216hrs for osimertinib post-dose

Study Arms (2)

Normal renal function

EXPERIMENTAL

For inclusion in the study as a patient with normal renal function, patients must have creatinine clearance ≥90 mL/min.

Drug: Osimertinib; AZD9291

Severe renal impairment

EXPERIMENTAL

For inclusion in the study as a patient with severe renal impairment, patients must have stable severe renal impairment (creatinine clearance \<30 mL/min), as defined by the Cockcroft Gault equation, for at least 2 months prior to Day 1.

Drug: Osimertinib; AZD9291

Interventions

Osimertinib; AZD9291 DRUG

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

Also known as: TAGRISSO™

Normal renal function; Severe renal impairment

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>18 years old
• Histological or cytological confirmation of a solid, malignant tumour (excluding lymphoma) that is refractory to standard therapies or for which no standard therapies exist. Tumours in which inhibition of the EGFR pathway is considered relevant by the Investigator are not mandated but are encouraged.
• ECOG performance status ≤2
• Life expectancy of ≥12 weeks
• BMI 18-35.
• Females should be using adequate contraceptive measures and must have a negative pregnancy test prior to dosing if of child-bearing potential or must have evidence of non-child bearing potential
• Males should use barrier contraception until 6 months after the last study drug is taken.

You may not qualify if:

• Participation in another clinical study with an IP during the last 14 days (or a longer period, depending on the agents used).
• Treatment with any of the following:
• Treatment with a 1st or 2nd generation EGFR-TKI within 8 days or approximately 5 half-lives, prior to the first dose of study drug.
• Any cytotoxic chemotherapy, investigational agents or anticancer drugs within 14 days of the first dose of study drug.
• Osimertinib in the present study or has previously received a 3rd generation EGFR-TKI (eg, CO 1686).
• Major surgery within 4 weeks of the first dose of study drug.
• Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment
• Currently receiving medications or herbal supplements known to be potent inducers of CYP3A4. Patients in Part B and continued access must avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known potent inducer effects on CYP3A4.
• Patients with severe renal impairment only: use of concurrent medication known to affect CrCl within 7 days of the first dose
• Unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment; with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy
• Spinal cord compression or brain metastases, unless asymptomatic, stable and not requiring steroids for at least 4 weeks prior to start of study treatment
• Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
• Absolute neutrophil count \<1.5 x 109/L
• Platelet count \<100 x 109/L
• Haemoglobin \<90 g/L

Sponsors & Collaborators

• AstraZeneca: lead
• Quintiles, Inc.: collaborator

Study Sites (11)

Research Site

Angers, 49055, France

Location

Research Site

Bordeaux, 33000, France

Location

Research Site

Dijon, 21079, France

Location

Research Site

Lille, 59020, France

Location

Research Site

Saint-Herblain, 44805, France

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Seoul, 05505, South Korea

Location

Research Site

Madrid, 28040, Spain

Location

Research Site

Madrid, 28046, Spain

Location

Research Site

Madrid, 28050, Spain

Location

Research Site

Seville, 41013, Spain

Location

Related Publications (1)

• Vishwanathan K, Sanchez-Simon I, Keam B, Penel N, de Miguel-Luken M, Weilert D, Mills A, Marotti M, Johnson M, Ravaud A. A multicenter, phase I, pharmacokinetic study of osimertinib in cancer patients with normal renal function or severe renal impairment. Pharmacol Res Perspect. 2020 Aug;8(4):e00613. doi: 10.1002/prp2.613.

  PMID: 32567817 DERIVED

MeSH Terms

Conditions

Renal Insufficiency

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Philippe Ravaud, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2016
• First Posted: October 5, 2016
• Study Start: May 4, 2017
• Primary Completion: September 20, 2018
• Study Completion: October 28, 2022
• Last Updated: November 27, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

FR (5); KR (2); ES (4)