Clinical Trials /

Study to Assess the Effect of AZD9291 on the Blood Levels of Rosuvastatin, in Patients With EGFRm+ Non-small Cell Lung Cancer

NCT02317016

Description:

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 rosuvastatin, following multiple oral dosing of AZD9291 in the 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 as a single agent until: disease progression; they are no longer deriving clinical benefit; or any other reason.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Study to Assess the Effect of AZD9291 on the Blood Levels of <span class="go-doc-concept go-doc-intervention">Rosuvastatin</span>, in Patients With EGFRm+ Non-small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span>

Title

  • Brief Title: Study to Assess the Effect of AZD9291 on the Blood Levels of Rosuvastatin, in Patients With EGFRm+ Non-small Cell Lung Cancer
  • Official Title: A Phase I, Open-Label, Non-Randomised, Multicentre Study to Assess the Effect of AZD9291 on the Pharmacokinetics of Rosuvastatin (a Sensitive BCRP Substrate) in Patients With EGFRm Positive NSCLC Whose Disease Has Progressed on an EGFR TKI
  • Clinical Trial IDs

    NCT ID: NCT02317016

    ORG ID: D5160C00019

    Trial Conditions

    Non Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    AZD9291 tablet dosing AZD9291 and rosuvastatin
    Rosuvastatin AZD9291 and rosuvastatin

    Trial Purpose

    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
    rosuvastatin, following multiple oral dosing of AZD9291 in the 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 as a single agent until: disease
    progression; they are no longer deriving clinical benefit; or any other reason.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    AZD9291 and rosuvastatin Experimental Sequential treatments of rosuvastatin alone followed by AZD9291 alone, followed by rosuvastatin + AZD9291. AZD9291 tablet dosing, Rosuvastatin

    Eligibility Criteria

    For inclusion in the study patients must fulfil the following criteria:

    1. Male or female, aged at least 18 years.

    2. Histological or cytological confirmation diagnosis of NSCLC.

    3. Radiological documentation of disease progression while on a previous continuous
    treatment with an EGFR TKI, eg, gefitinib, erlotinib or afatinib. In addition, other
    lines of therapy may have been given. All patients must have documented radiological
    progression on the last treatment administered prior to enrolling in the study.

    4. Confirmation that the tumour harbours an EGFR mutation known to be associated with
    EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q).

    5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no
    deterioration over the previous 2 weeks (Appendix G).

    6. Patients must have a life expectancy of 12 weeks as estimated at the time of
    screening.

    7. Females should be using adequate contraceptive measures and must have a negative
    pregnancy test prior to start of dosing if of child-bearing potential, or must have
    evidence of non-child-bearing potential by fulfilling one of the following criteria
    at screening: Post-menopausal defined as aged more than 50 years and amenorrhoeic for
    at least 12 months following cessation of all exogenous hormonal treatments; Women
    under 50 years old would be considered post-menopausal if they have been amenorrhoeic
    for 12 months or more following cessation of exogenous hormonal treatments and with
    luteinising hormone (LH) and follicle stimulating hormone (FSH) levels in the
    post-menopausal range for the institution; Documentation of irreversible surgical
    sterilisation by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy,
    but not tubal ligation.

    8. Patients are willing and able to comply with the protocol for the duration of the
    study including undergoing treatment and scheduled visits and examinations.

    9. Male patients should be willing to use barrier contraception, ie, condoms.

    Exlusion Criteria:

    1. Participation in another clinical study with an IP in last 14 days (or longer
    depending on the defined characteristics of the agents used).

    2. Any patient of Asian ethnicity or has a parent who is of Asian ethnicity (eg,
    Chinese, Filipino, Japanese, Korean and Vietnamese). If only a grandparent is Asian,
    this is acceptable. Asian Indians are acceptable.

    3. Treatment w/ any of the following: an EGFR TKI (eg, erlotinib, gefitinib or afatinib)
    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 of study treatment; Major surgery (excluding placement of vascular
    access) w/in 4 weeks of the 1st dose of study treatment; Radiotherapy with a limited
    field of radiation for palliation w/in 1 week of the first dose of study treatment,
    with the exception of patients receiving radiation to more than 30% of bone marrow or
    with a wide field of radiation which must be completed w/in 4 weeks of the 1st dose
    of study treatment; 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.

    4. Unresolved toxicities from prior therapy > CTCAE Grade 1 at the study start besides
    alopecia and Grade 2, prior platinum-therapy related neuropathy.

    5. 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 35
    of Part A.

    6. Spinal cord compression or brain metastases unless asymptomatic, stable and not
    requiring steroids for at least 4 weeks prior to start of study treatment.

    7. 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 hep B, hep C and HIV.
    Screening for chronic conditions is not required.

    8. 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; 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.

    9. 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 40 years of age or any concomitant medication known to prolong the QT
    interval

    10. Patients unable to swallow orally administered medication or patients with
    gastrointestinal disorders or significant gastrointestinal resection likely to
    interfere with the absorption of AZD9291.

    11. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required
    steroid treatment, or any evidence of clinically active ILD.

    12. Women who are breastfeeding.

    13. Patients with a known hypersensitivity to AZD9291 or rosuvastatin or any of the
    excipients of the products.

    14. Concomitant medication contraindicated for use with rosuvastatin due to drug
    interaction and/or associated with increased risk of rhabdomyolysis (including, but
    not limited to): fibrates (eg, gemfibrozil, fenofibrate), niacin, cyclosporine,
    lopinavir/ritonavir or atazanavir/ritonavir and colchinine.

    15. Past medical history of drug-related rhabdomyolysis and/or myalgia.

    16. Use of 3-hydroxy-3-methyl-glutaryl coenzyme A-reductase inhibitors, such as
    lovastatin and simvastatin (Part A only).

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Maximum plasma concentration (Cmax) of rosuvastatin

    Area under the plasma concentration time curve from zero to infinity (AUC) of rosuvastatin

    Secondary Outcome Measures

    t(max) of rosuvastatin

    AUC(0-t) of rosuvastatin

    CL/F of rosuvastatin

    Vz/F of rosuvastatin

    z of rosuvastatin

    t(1/2) of rosuvastatin

    AUC(tau) of AZD9291, AZ5104 and AZ7550

    Css(max) of AZD9291, AZ5104 and AZ7550

    tss(max) of AZD9291, AZ5104 and AZ7550

    Css(min) of AZD9291, AZ5104 and AZ7550

    CLss/F of AZD9291

    MR ratios of AUC (MRAUC(tau)) of AZ5104 and AZ7550

    MR ratios of Css,max (MR(Css,max)) of AZ5104 and AZ7550

    Assessment of the safety and tolerability of AZD9291

    Trial Keywords

    oncology

    cancer

    non small cell lung cancer

    anticancer drug

    pharmacokinetics

    AZD9291

    rosuvastatin

    EGFR genes