Study to Assess the Effect of Osimertinib (TAGRISSO™ ) on Blood Levels of Fexofenadine in Patients With EGFRm+ NSCLC

NCT02908750 | Completed Phase 1

• 1 other identifier: D5160C00036
• Study Type: interventional
• Target: 24
• Locations: 3 countries
• Sites: 7

Brief Summary

This is a Phase I, open-label, 2-part study in patients with a confirmed diagnosis of epidermal growth factor receptor (EGFR) mutation positive (EGFRm+) non-small cell lung cancer (NSCLC), who have progressed following prior therapy with an approved EGFR tyrosine kinase inhibitor (TKI) agent. Part A will assess the effect of osimertinib on the pharmacokinetic (PK) parameters of fexofenadine, following single and multiple oral dosing of osimertinib in a fasted state. Continuous Access will allow patients further access to osimertinib after the PK phase (Part A). All patients from Part A who completed treatment may continue to receive osimertinib 80 mg once daily until: they are no longer deriving clinical benefit; or any other reason

Conditions

Non Small Cell Lung Cancer

Keywords

oncology; cancer; non small cell lung cancer; anticancer drug; lung neoplasms; pharmacokinetics; AZD9291; osimertinib; fexofenadine; TAGRISSO™; EGFR genes

Outcome Measures

Primary Outcomes (2)

• Fexofenadine Cmax (alone and in combination with osimertinib)

  To characterize the pharmacokinetics of fexofenadine by assessment of maximum plasma fexofenadine concentration.

  Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 36, 48, 60, 72 on Day 1 in Period 1 and Day 1 and Day 39 in Period 2

• Fexofenadine AUC (alone and in combination with osimertinib)

  To characterize the pharmacokinetics of fexofenadine by assessment of area under the plasma concentration time curve from zero to infinity

  Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 36, 48, 60, 72 on Day 1 in Period 1 and Day 1 and Day 39 in Period 2.

Secondary Outcomes (23)

• Fexofenadine tmax (alone and in combination with osimertinib)

  Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10 24, 36, 48, 60, 72 on Day 1 in Period 1 and Day 1 and Day 39 in Period 2

• Fexofenadine AUC0-t (alone and in combination with osimertinib)

  Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10 24, 36, 48, 60, 72 on Day 1 in Period 1 and Day 1 and Day 39 in Period 2

• Fexofenadine CL/F (alone and in combination with osimertinib)

  Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10 24, 36, 48, 60, 72 on Day 1 in Period 1 and Day 1 and Day 39 in Period 2

• Fexofenadine Vz/F (alone and in combination with osimertinib)

  Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10 24, 36, 48, 60, 72 on Day 1 in Period 1 and Day 1 and Day 39 in Period 2

• Fexofenadine λz (alone and in combination with osimertinib)

  Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10 24, 36, 48, 60, 72 on Day 1 in Period 1 and Day 1 and Day 39 in Period 2

Study Arms (1)

osimertinib and fexofenadine

EXPERIMENTAL

Sequential treatments of fexofenadine alone followed by osimertinib + fexofenadine, followed by osimertinib alone, followed by osimertinib + fexofenadine

Drug: Fexofenadine tablet dosing; Drug: Osimertininb tablet dosing

Interventions

Fexofenadine tablet dosing DRUG

Fexofenadine (P-gp substrate) 120mg taken once daily on Days 1 in Treatment Period 1 and Day 1 and Day 39 in Treatment Period 2

Also known as: Mucinex, Allegra, Select, Rugby

osimertinib and fexofenadine

Osimertininb tablet dosing DRUG

Osimertininb 80 mg taken once daily on Day 1 and Days 4 to 41 in Treatment Period 2

Also known as: TAGRISSO™

osimertinib and fexofenadine

Eligibility Criteria

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

You may qualify if:

• Male or female, ≥18 years
• Histological or cytological confirmation diagnosis of NSCLC
• Radiological documentation of disease progression while receiving previous continuous treatment with an EGFR-TKI.
• Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR-TKI sensitivity
• ECOG performance status 0 to 1, with no deterioration over the previous 2 weeks.
• Patients must have a life expectancy of 12 weeks or longer
• Females should be using adequate contraceptive measures and must have a negative serum pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child bearing potential.
• Male patients should be willing to use barrier contraception ie, condoms until 6 months after the last study drug is taken.

You may not qualify if:

• Treatment with any of the following:
• A 1st or 2nd generation EGFR-TKI within 8 days or approximately 5 half-lives, of the first dose of study treatment
• Osimertinib in the present study \[ie, dosing with osimertinib previously initiated in this study\] or has previously received a 3rd generation EGFR-TKI \[eg, CO 1686\].
• Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
• Major surgery \[excluding placement of vascular access\] within 4 weeks of the first dose of study treatment.
• Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment
• Patients currently receiving \[or unable to stop at least 3 weeks prior to first dose of osimertinib\] medications or herbal supplements known to be potent inducers of CYP3A4 or inducers/inhibitors of P-gp.
• Spinal cord compression or brain metastases, unless asymptomatic, stable and not requiring steroids for at least 4 weeks prior to start of study treatment.
• Any of the following cardiac criteria:
• Mean resting corrected QT interval corrected for heart rate using Fridericia's correction factor \[QTcF\] greater than 470 msec, obtained from 3 ECGs.
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG \[eg, complete left bundle branch block, third degree heart block, second degree heart block, PR interval greater than 250 msec\]
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
• Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
• Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
• Absolute neutrophil count \[ANC\] less than 1.5 × 109/L

Sponsors & Collaborators

• AstraZeneca: lead
• Quintiles, Inc.: collaborator

Study Sites (7)

Research Site

Rennes, 35033, France

Location

Research Site

Seongnam-si, 13620, 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)

• Calvo E, Lee JS, Kim SW, Moreno V, deCastro Carpeno J, Weilert D, Laus G, Mann H, Vishwanathan K. Modulation of Fexofenadine Pharmacokinetics by Osimertinib in Patients With Advanced EGFR-Mutated Non-Small Cell Lung Cancer. J Clin Pharmacol. 2019 Aug;59(8):1099-1109. doi: 10.1002/jcph.1403. Epub 2019 Mar 15.

  PMID: 30875094 DERIVED

Related Links

• Redacted CSP

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms; Lung Neoplasms

Interventions

Acetylcysteine; fexofenadine; osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Emiliano C Aller, M.D., Ph.D.

  Centro Integral Oncologico Clara Campal

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 23, 2016
• First Posted: September 21, 2016
• Study Start: March 2, 2017
• Primary Completion: July 31, 2017
• Study Completion: October 11, 2022
• Last Updated: November 14, 2022

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

KR (2); FR (1); ES (4)