Non Small Cell Lung CancerPhase 1NCT02908750
Study to Assess the Effect of Osimertinib (TAGRISSO™ ) on Blood Levels of Fexofenadine in Patients With EGFRm+ NSCLC
A Phase 1 study testing Fexofenadine tablet dosing and Osimertininb tablet dosing in people with Non Small Cell Lung Cancer, run by AstraZeneca at 7 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- Fexofenadine tablet dosing and Osimertininb tablet dosing
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 7 sitesin 3 countries
- Study dates
- 2 Mar 2017to 11 Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
- For inclusion in optional genetic research, patients must provide separate informed consent.
Who cannot join
- 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
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- 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
- Platelet count less than 100 × 109/L
- Haemoglobin less than 90 g/L
- ALT greater than 2.5 times ULN if no demonstrable liver metastases or greater than 5 times ULN in the presence of liver metastases
- AST greater than 2.5 times ULN if no demonstrable liver metastases or greater than 5 times ULN in the presence of liver metastases
- Total bilirubin greater than 1.5 times ULN if no liver metastases or greater than 3 times ULN in the presence of liver metastases
- Creatinine greater than 1.5 times institutional ULN concurrent with creatinine clearance less than 50 mL/min [measured or calculated by Cockcroft-Gault formula]
- Patients unable to swallow orally administered medication or with gastrointestinal disorders or significant gastrointestinal resection likely to interfere with the absorption of the study drugs.
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
Spain4 sites
Research Site
Madrid, 28040
Research Site
Madrid, 28046
Research Site
Madrid, 28050
Research Site
Seville, 41013
South Korea2 sites
Research Site
Seongnam-si, 13620
Research Site
Seoul, 05505
About this study
Official title: An Open-label, Non-randomised, Phase I Study to Assess the Effect of Single and Multiple Oral Doses of Osimertinib (TAGRISSO™) on the Pharmacokinetics of a P-glycoprotein Probe Drug (Fexofenadine) in Patients With Advanced EGFRm NSCLC That Have Progressed on a Prior EGFR-TKI Regimen
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
Read the detailed description
This is a Phase I, open-label, non-randomised, two-part study in patients with EGFRm+ NSCLC who have progressed on an EGFR-TKI.
The PK phase will assess the effect of osimertinib on the PK parameters of fexofenadine following both single and multiple oral dosing of osimertinib. Continued access will provide patients with further access to osimertinib after the PK phase.
The study will be conducted at approximately 10 sites across Asia and Western Europe, with approximately 24 patients enrolled in order to achieve at least 18 evaluable patients. Additional patients may be dosed to ensure the minimum number of evaluable patients.
PK phase The PK phase is a non-randomised, open-label, 2-period design. Treatment Period 1 and Treatment Period 2 are separated by a 3 to 7 day washout period between doses. A study flow chart for the PK phase is presented in Figure 1. Patients will receive osimertinib 80 mg as a single dose on Day 1 of Treatment Period 2, then 80 mg once daily for 38 days (from Day 4 to Day 41 in Treatment Period 2). Patients will also receive a single oral dose of fexofenadine on Day 1 in Treatment Period 1, and on Days 1 and 39 in Treatment Period 2.
Continued access On completion of the PK phase (ie, following collection of the 72-hour fexofenadine sample on Day 42), patients may continue to take osimertinib tablets (80 mg once daily) as a single agent in continued access if they and the Investigator agree that this is appropriate. This will continue until the Investigator believes they are no longer deriving clinical benefit, or they stop taking osimertinib for any other reason. No clinical data will be collected during this phase other than sudden death of unknown reason, serious adverse events (SAEs) that may be related to osimertinib, outcomes of pregnancy and drug dispensing/accountability.
If a patient discontinues treatment during the PK phase, they will return to the clinic for follow-up assessments 30 days (±7 days) after their last dose of treatment in the PK phase. If the patient's last dose of osimertinib is in continued access, the patient should be contacted 30 days after their last dose of osimertinib to follow-up any existing SAEs, monitor for new SAEs that may be related to the IP, and record any sudden deaths of unknown cause.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- Fexofenadine tablet dosing, Osimertininb tablet dosing
- Keywords
- oncology, cancer, non small cell lung cancer, anticancer drug, lung neoplasms, pharmacokinetics, AZD9291, osimertinib, fexofenadine, TAGRISSO™, EGFR genes
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasms, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fexofenadine tablet dosingDrug
Also called Mucinex, Allegra, Select, Rugby
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
Osimertininb tablet dosingDrug
Also called TAGRISSO™
Osimertininb 80 mg taken once daily on Day 1 and Days 4 to 41 in Treatment Period 2
| Study group | Role | What they receive |
|---|---|---|
| osimertinib and fexofenadine | Experimental | Sequential treatments of fexofenadine alone followed by osimertinib + fexofenadine, followed by osimertinib alone, followed by osimertinib + fexofenadine Receives: Drug: Fexofenadine tablet dosing; Drug: Osimertininb tablet dosing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fexofenadine Cmax (alone and in combination with osimertinib)
To characterize the pharmacokinetics of fexofenadine by assessment of maximum plasma fexofenadine concentration.
Measured: 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
Measured: 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)
To characterize the pharmacokinetics of fexofenadine by assessment of time to reach maximum plasma concentration
Measured: 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)
To characterize the pharmacokinetics of fexofenadine by assessment of area under plasma concentration-time curve from time zero to the last quantifiable time point
Measured: 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)
To characterize the pharmacokinetics of fexofenadine by assessment of apparent plasma clearance following oral administration
Measured: 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)
To characterize the pharmacokinetics of fexofenadine by assessment of apparent volume of distribution
Measured: 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)
To characterize the pharmacokinetics of fexofenadine by assessment of terminal rate constant
Measured: 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 t½λz (alone and in combination with osimertinib)
To characterize the pharmacokinetics of fexofenadine by assessment of terminal half-life
Measured: 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
Osimertinib and metabolites (AZ5104 and AZ7550)
To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of trough concentrations
Measured: Blood samples are collected pre-dose on D11, D18, D25, and D32
Osimertinib and metabolites (AZ5104 and AZ7550) single dose: AUC0-72
To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of area under plasma concentration-time curve from time zero to 72 hours post-dose
Measured: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24, 36, 48, 60, 72 on Day 1 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) single dose: Cmax
To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of maximum plasma drug concentration
Measured: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24, 36, 48, 60, 72 on Day 1 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) single dose: tmax
To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of Time to reach maximum plasma concentration
Measured: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24, 36, 48, 60, 72 on Day 1 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) single dose: MRCmax
To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of metabolite to parent ratio (AZ5104:osimertinib, AZ7550:osimertinib) maximum plasma drug concentration
Measured: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24, 36, 48, 60, 72 on Day 1 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) multiple dose: AUCtau
To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of area under plasma concentration time curve during the dosing interval
Measured: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24 on Day 39 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) multiple dose Css,max
To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of maximum plasma concentration at steady state
Measured: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24 on Day 39 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) multiple dose Css,min
To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of minimum plasma concentration at steady state
Measured: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24 on Day 39 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) multiple dose: CLss/F (osimertinib only)
To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of apparent plasma clearance following oral administration at steady state
Measured: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24 on Day 39 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) multiple doses: MRAUCtau
To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of metabolite to parent ratio (AZ5104:osimertinib, AZ7550:osimertinib) area under plasma concentration time curve during the dosing interval
Measured: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24 on Day 39 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) multiple dose: MRCss,max
To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of metabolite to parent ratio (AZ5104:osimertinib, AZ7550:osimertinib) maximum plasma concentration at steady state
Measured: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24 on Day 39 in Period 2
Safety data collected using: Assessment of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Measured: Part A, approximately 11 weeks
Safety data collected using: Assessment of serious adverse events (SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) (Version 4)
Measured: Part A and Continuous Access, approximately 24 months
Safety data collected using: vital signs (blood pressure, pulse, temperature, height, weight)
Measured: Part A, approximately 11 weeks
Safety data collected using: laboratory parameters (clinical chemistry, heamatology, urinalysis)
Measured: Part A, approximately 11 weeks
Safety data collected using: physical examination
Measured: Part A, approximately 11 weeks
Safety data collected using: standard 12-lead electrocardiograms (ECGS)
Measured: Part A, approximately 11 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2016 (estimated)
- Study start2 Mar 2017
- Primary completion31 Jul 2017
- Study completion11 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Quintiles, Inc.
- Responsible party
- Sponsor
- Investigators
- Emiliano C Aller, M.D., Ph.D., Principal investigator, Centro Integral Oncologico Clara Campal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02908750
- Sponsor's protocol ID
- D5160C00036
- Status last verified
- Nov 2022
- First submitted
- 23 Aug 2016
- Last updated
- 14 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Publications
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.
PubMed 30875094
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Non-randomised, Phase I Study to Assess the Effect of Single and Multiple Oral Doses of Osimertinib (TAGRISSO™) on the Pharmacokinetics of a P-glycoprotein Probe Drug (Fexofenadine) in Patients With Advanced EGFRm NSCLC That Have Progressed on a Prior EGFR-TKI Regimen
- ClinicalTrials.gov ID
- NCT02908750
- Acronym / sponsor ID
- D5160C00036
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- oncology, cancer, non small cell lung cancer, anticancer drug, lung neoplasms, pharmacokinetics, AZD9291, osimertinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Quintiles, Inc.
- Study start
- 2 Mar 2017 (actual)
- Primary completion
- 31 Jul 2017 (actual)
- Study completion
- 11 Oct 2022 (actual)
- First posted
- 21 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
This is a Phase I, open-label, non-randomised, two-part study in patients with EGFRm+ NSCLC who have progressed on an EGFR-TKI.
The PK phase will assess the effect of osimertinib on the PK parameters of fexofenadine following both single and multiple oral dosing of osimertinib. Continued access will provide patients with further access to osimertinib after the PK phase.
The study will be conducted at approximately 10 sites across Asia and Western Europe, with approximately 24 patients enrolled in order to achieve at least 18 evaluable patients. Additional patients may be dosed to ensure the minimum number of evaluable patients.
PK phase The PK phase is a non-randomised, open-label, 2-period design. Treatment Period 1 and Treatment Period 2 are separated by a 3 to 7 day washout period between doses. A study flow chart for the PK phase is presented in Figure 1. Patients will receive osimertinib 80 mg as a single dose on Day 1 of Treatment Period 2, then 80 mg once daily for 38 days (from Day 4 to Day 41 in Treatment Period 2). Patients will also receive a single oral dose of fexofenadine on Day 1 in Treatment Period 1, and on Days 1 and 39 in Treatment Period 2.
Continued access On completion of the PK phase (ie, following collection of the 72-hour fexofenadine sample on Day 42), patients may continue to take osimertinib tablets (80 mg once daily) as a single agent in continued access if they and the Investigator agree that this is appropriate. This will continue until the Investigator believes they are no longer deriving clinical benefit, or they stop taking osimertinib for any other reason. No clinical data will be collected during this phase other than sudden death of unknown reason, serious adverse events (SAEs) that may be related to osimertinib, outcomes of pregnancy and drug dispensing/accountability.
If a patient discontinues treatment during the PK phase, they will return to the clinic for follow-up assessments 30 days (±7 days) after their last dose of treatment in the PK phase. If the patient's last dose of osimertinib is in continued access, the patient should be contacted 30 days after their last dose of osimertinib to follow-up any existing SAEs, monitor for new SAEs that may be related to the IP, and record any sudden deaths of unknown cause.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| osimertinib and fexofenadine | Experimental | Drug: Fexofenadine tablet dosing, Drug: Osimertininb tablet dosingSequential treatments of fexofenadine alone followed by osimertinib + fexofenadine, followed by osimertinib alone, followed by osimertinib + fexofenadine |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (22 listed)
- Treatment with any of the following:
- 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:
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fexofenadine tablet dosingAlso: Mucinex, Allegra, Select, RugbyFexofenadine (P-gp substrate) 120mg taken once daily on Days 1 in Treatment Period 1 and Day 1 and Day 39 in Treatment Period 2 | Drug | osimertinib and fexofenadine |
| Osimertininb tablet dosingAlso: TAGRISSO™Osimertininb 80 mg taken once daily on Day 1 and Days 4 to 41 in Treatment Period 2 | Drug | osimertinib and fexofenadine |
Primary outcome
Fexofenadine Cmax (alone and in combination with osimertinib)
Time frame: 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
To characterize the pharmacokinetics of fexofenadine by assessment of maximum plasma fexofenadine concentration.
Fexofenadine AUC (alone and in combination with osimertinib)
Time frame: 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.
To characterize the pharmacokinetics of fexofenadine by assessment of area under the plasma concentration time curve from zero to infinity
23 secondary outcomes
Fexofenadine tmax (alone and in combination with osimertinib)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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 t½λz (alone and in combination with osimertinib)
Time frame: 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
Osimertinib and metabolites (AZ5104 and AZ7550)
Time frame: Blood samples are collected pre-dose on D11, D18, D25, and D32
Osimertinib and metabolites (AZ5104 and AZ7550) single dose: AUC0-72
Time frame: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24, 36, 48, 60, 72 on Day 1 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) single dose: Cmax
Time frame: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24, 36, 48, 60, 72 on Day 1 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) single dose: tmax
Time frame: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24, 36, 48, 60, 72 on Day 1 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) single dose: MRCmax
Time frame: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24, 36, 48, 60, 72 on Day 1 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) multiple dose: AUCtau
Time frame: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24 on Day 39 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) multiple dose Css,max
Time frame: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24 on Day 39 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) multiple dose Css,min
Time frame: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24 on Day 39 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) multiple dose: CLss/F (osimertinib only)
Time frame: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24 on Day 39 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) multiple doses: MRAUCtau
Time frame: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24 on Day 39 in Period 2
Osimertinib and metabolites (AZ5104 and AZ7550) multiple dose: MRCss,max
Time frame: Blood samples are collected pre-dose, 1, 2, 3, 4, 5, 6, 8, 10 24 on Day 39 in Period 2
Safety data collected using: Assessment of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Time frame: Part A, approximately 11 weeks
Safety data collected using: Assessment of serious adverse events (SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) (Version 4)
Time frame: Part A and Continuous Access, approximately 24 months
Safety data collected using: vital signs (blood pressure, pulse, temperature, height, weight)
Time frame: Part A, approximately 11 weeks
Safety data collected using: laboratory parameters (clinical chemistry, heamatology, urinalysis)
Time frame: Part A, approximately 11 weeks
Safety data collected using: physical examination
Time frame: Part A, approximately 11 weeks
Safety data collected using: standard 12-lead electrocardiograms (ECGS)
Time frame: Part A, approximately 11 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2022.
- Derived from this study: PubMed 30875094Calvo 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.
- Redacted CSPLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emiliano C Aller, M.D., Ph.D. principal investigator
Centro Integral Oncologico Clara Campal
7 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fexofenadine tablet dosing and Osimertininb tablet dosing in people with Non Small Cell Lung Cancer, run by AstraZeneca at 7 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Spain, South Korea, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fexofenadine Cmax (alone and in combination with osimertinib) (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02908750, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2022.