AzTrials
AzTrials

Non Small Cell Lung CancerPhase 1NCT02197234

Study to Assess the Effect of AZD9291 on the Blood Levels of Simvastatin in Patients With EGFRm+ NSCLC

A Phase 1 study testing Pharmacokinetic sampling - AZD9291, Simvastatin and AZD9291 tablet dosing in people with Non Small Cell Lung Cancer, run by AstraZeneca at 16 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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?
Pharmacokinetic sampling - AZD9291, Simvastatin and AZD9291 tablet dosing
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
16 sitesin 5 countries
Study dates
22 Dec 2014to 3 Jun 2024
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

None listed.

Who cannot join

  • Participation in another study with an IP during the last 14 days (or a longer period depending on the defined characteristics of the agents used).
  • Treatment with any of the following: Treatment with an EGFR TKI (eg, erlotinib or gefitinib) within 8 days or approx. 5 x half-life, whichever is the longer, of the first dose of study treatment; any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose; 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, with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation which must be completed within 4 weeks of the first dose; patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inhibitors of CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior). All patients must avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer/inhibitory effects on CYP3A4.
  • Any 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.
  • Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of the IP until the final PK sample collection on Day 32 of Part A.
  • 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 evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the PI's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C, and HIV. Screening for chronic conditions not required.
Show all 15Show fewer
  • Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: ANC <1.5 x 10^9/L; platelet count <100 x 10^9/L; haemoglobin <90 g/L; ALT >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases; Aspartate aminotransferase (AST) >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases; total bilirubin >1.5 times ULN if no liver metastases or >3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases; creatinine >1.5 times ULN concurrent with creatinine clearance <50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN.
  • Any of the following cardiac criteria: mean resting corrected QT interval corrected for heart rate using Fridericia's correction factor (QTcF) >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 >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 age of 40 or any concomitant medication known to prolong the QT interval.
  • Patients unable to swallow oral medication or patients with GI disorders or significant GI resection likely to interfere with the absorption of AZD9291.
  • Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
  • Women who are breastfeeding.
  • Patients with a known hypersensitivity to AZD9291, simvastatin, or any of the excipients of the products.
  • Concomitant medication contraindicated for use with simvastatin due to drug interaction associated with increased risk of rhabdomyolysis (including, but not limited to): itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors (eg, nelfinavir), nefazodone, cyclosporine, danazol, gemfibrozil, amiodarone, amlodipine.
  • 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA)-reductase inhibitors, such as lovastatin and simvastatin.
  • For optional genetic research: Previous allogenic bone marrow transplant or non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.

Trial locations and contacts

16 sites in 5 countries.

16 sites in 5 countries

France5 sites

  • Research Site

    Angers, 49055

  • Research Site

    Dijon, 21079

  • Research Site

    Marseille, 13385

  • Research Site

    Rennes, 35033

  • Research Site

    Saint-Herblain, 44805

Other trials in France

South Korea5 sites

  • Research Site

    Seongnam-si, 13620

  • Research Site

    Seoul, 03080

  • Research Site

    Seoul, 03722

  • Research Site

    Seoul, 05505

  • Research Site

    Seoul, 06351

Other trials in South Korea

Spain4 sites

  • Research Site

    Badalona, 08916

  • Research Site

    Barcelona, 08041

  • Research Site

    Madrid, 28046

  • Research Site

    Seville, 41013

Other trials in Spain

United States1 site

  • Research Site

    Atlanta, Georgia, 30322

Other trials in United States

Belgium1 site

  • Research Site

    Leuven, 3000

Other trials in Belgium

About this study

Official title: A Phase I, Open-Label, Non-Randomised, Multicentre Study to Assess the Effect of AZD9291 on the Pharmacokinetics of Simvastatin (a Sensitive CYP3A4 Substrate) in Patients With EGFRm Positive NSCLC Whose Disease Has Progressed on an EGFR TKI

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 AZD9291 on the pharmacokinetic (PK) parameters of simvastatin and simvastatin acid, following multiple oral dosing of AZD9291 in a fasted state.

Part B will allow patients further access to AZD9291 after the PK phase (Part A) and will provide for additional safety data collection. All patients from Part A who completed treatment may continue to receive AZD9291 80 mg once daily until: disease progression; they are no longer deriving clinical benefit; or any other reason.

Being tested
Pharmacokinetic sampling - AZD9291, Simvastatin, AZD9291 tablet dosing, Pharmacokinetic sampling - simvastatin, Pharmacokinetic sampling - AZ5140 and AZ7550
Keywords
oncology, cancer, non small cell lung cancer, anticancer drug, pharmacokinetics, AZD9291, simvastatin, EGFR genes
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pharmacokinetic sampling - AZD9291Procedure or surgery

    Blood sampling to measure AZD9291

  • SimvastatinDrug

    Simvastatin (CYP substrate) 40mg taken once daily on Days 1 and 31 (Part A)

  • AZD9291 tablet dosingDrug

    AZD9291 80mg tablet taken from Days 3 to 32. (Part B) AZD9291 80mg tablet taken daily for 12 months.

  • Pharmacokinetic sampling - simvastatinProcedure or surgery

    Blood sampling to measure simvastatin levels

  • Pharmacokinetic sampling - AZ5140 and AZ7550Procedure or surgery

    Blood samples to measure levels of AZ5140 and AZ7550

Study groups in NCT02197234
Study groupRoleWhat they receive
AZD9291 and simvastatinExperimentalSequential treatments of simvastatin alone followed by AZD9291 alone, followed by simvastatin + AZD9291.
Receives: Procedure: Pharmacokinetic sampling - AZD9291; Drug: Simvastatin; Drug: AZD9291 tablet dosing; Procedure: Pharmacokinetic sampling - simvastatin; Procedure: Pharmacokinetic sampling - AZ5140 and AZ7550

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cmax of Simvastatin

    Pharmacokinetics of simvastatin by assessment of maximum plasma simvastatin concentration

    Measured: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A

  2. AUC of Simvastatin

    Pharmacokinetics of simvastatin by assessment of area under the plasma concentration time curve from zero to infinity

    Measured: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A

Secondary outcomes (5)

  1. Tmax of Simvastatin and Simvastatin Acid

    Pharmacokinetics of simvastatin and simvastatin acid by time to Cmax

    Measured: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A

  2. CL/F of Simvastatin

    Rate and extent of absorption of simvastatin by assessment of apparent clearance following oral administration

    Measured: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A

  3. Cmax of Simvastatin Acid

    Pharmacokinetics of simvastatin acid by assessment of maximum plasma simvastatin acid concentration

    Measured: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A

  4. AUC of Simvastatin Acid

    Pharmacokinetics of simvastatin acid by assessment of area under the plasma concentration time curve from zero to infinity

    Measured: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A

  5. AUC(0-t) of Simvastatin and Simvastatin Acid

    Pharmacokinetics of simvastatin and simvastatin acid by assessment of area under the plasma concentration time curve from time zero to last quantifiable dose

    Measured: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jul 2014 (estimated)
  2. Study start22 Dec 2014
  3. Primary completion30 Apr 2015
  4. Study completion3 Jun 2024

Resources

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
Not applicable
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02197234
Sponsor's protocol ID
D5160C00014
Other IDs
2014-002070-36, 2014
Status last verified
Nov 2025
First submitted
21 Jul 2014
Last updated
20 Nov 2025
Data monitoring committee
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

  • Harvey RD, Aransay NR, Isambert N, Lee JS, Arkenau T, Vansteenkiste J, Dickinson PA, Bui K, Weilert D, So K, Thomas K, Vishwanathan K. Effect of multiple-dose osimertinib on the pharmacokinetics of simvastatin and rosuvastatin. Br J Clin Pharmacol. 2018 Dec;84(12):2877-2888. doi: 10.1111/bcp.13753. Epub 2018 Oct 10.

    PubMed 30171779

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pharmacokinetic sampling - AZD9291, Simvastatin and AZD9291 tablet dosing in people with Non Small Cell Lung Cancer, run by AstraZeneca at 16 sites in 5 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 0 inclusion and 15 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 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in France, South Korea, Spain, United States, Belgium. 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?

Yes. Results are posted in the registry (first posted 22 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Cmax of Simvastatin (time frame: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A). 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 NCT02197234, 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 20 Nov 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in