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Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors, AZD3759 or AZD9291, in Patients Who Have Advanced Non-Small Cell Lung Cancer

NCT02228369

Description:

This is the first time in patient study to assess the safety, tolerability and preliminary efficacy of AZD3759 in patients with advanced Non Small Cell Lung Cancer (NSCLC) In this study, patients with Leptomeningeal Metastasis and Brain Metastasis may also be enrolled to assess the anti-tumour efficacy, safety, pharmacokinetics and potential biological activity of AZD9291

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

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors, AZD3759 or AZD9291, in Patients Who Have Advanced Non-Small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span>

Title

  • Brief Title: Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors, AZD3759 or AZD9291, in Patients Who Have Advanced Non-Small Cell Lung Cancer
  • Official Title: A Phase I, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-Tumour Activity of AZD3759 or AZD9291 in Patients With EGFR Mutation Positive Advanced Stage Non Small Cell Lung Cancer (NSCLC)
  • Clinical Trial IDs

    NCT ID: NCT02228369

    ORG ID: D6030C00001

    Trial Conditions

    EGFR Mutation Positive Advanced Non Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    AZD3759 Daily dose of AZD3759
    AZD9291 Daily Dose of AZD9291

    Trial Purpose

    This is the first time in patient study to assess the safety, tolerability and preliminary
    efficacy of AZD3759 in patients with advanced Non Small Cell Lung Cancer (NSCLC) In this
    study, patients with Leptomeningeal Metastasis and Brain Metastasis may also be enrolled to
    assess the anti-tumour efficacy, safety, pharmacokinetics and potential biological activity
    of AZD9291

    Detailed Description

    A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability,
    Pharmacokinetics and Preliminary Anti-Tumour Activity of AZD3759 or AZD9291 in Patients with
    EGFR Mutation Positive Advanced Stage Non Small Cell Lung Cancer (NSCLC) who failed standard
    treatment and developed brain or leptomeningeal diseases

    Trial Arms

    Name Type Description Interventions
    Daily dose of AZD3759 Experimental Daily oral dose of AZD3759 AZD3759
    Daily Dose of AZD9291 Experimental Daily oral dose of AZD9291 AZD9291

    Eligibility Criteria

    Inclusion Criteria:

    1. Obtained written informed consent

    2. Male or female aged at least 18 years. Aged at least 20 if Japanese.

    3. Histologically or cytologically confirmed diagnosis of NSCLC with single activating
    EGFR mutations (L858R or Exon19Del).

    4. Eastern Cooperative Oncology Group performance status of 0 to1. For LM patients, 0 to
    2 is acceptable.

    5. In Part A, prior treatment with at least one line of a single agent EGFR TKI and at
    least 1 line of chemotherapy.

    6. In Part B-BM expansion, progressed intracranially following immediate prior treatment
    of an EGFR TKI but with stable extracranial disease. For Part B-LM expansion,
    patients who received previous EGFR TKI treatment must have stable extracranial
    disease;EGFR TKI treatment nave patients can also be enrolled into AZD9291 cohorts,
    or AZD3759 cohorts if efficacy signal seen in Part A and agreed by Safety Review
    Committee.

    7. For patients with neither LM nor measurable BM: At least one measurable extracranial
    lesion. For patients with measurable BM but without LM: at least one measurable
    intracranial lesion

    8. For patients with LM: Confirmed diagnosis of LM by positive CSF cytology.

    9. Male patients should be willing to use barrier contraception, i.e., condoms, until 3
    months after last study drug is taken.

    10. Females should agree to use adequate contraceptive measures, should not be breast
    feeding 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

    Exclusion Criteria:

    1. For patients with LM and/or BM, CNS complications that require urgent neurosurgical
    intervention

    2. For patient with LM, inability to undergo collection of CSF

    3. Treatment with an EGFR TKI (e.g., erlotinib or gefitinib) within 8 days or
    approximately 5 x half-life, whichever is the longer, of the first dose of study
    treatment.

    4. Any cytotoxic chemotherapy,or other anticancer drugs for the treatment of advanced
    NSCLC from a previous treatment regimen within 14 days of the first dose of study
    treatment

    5. Radiotherapy with a wide field of radiation within 4 weeks or 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 which must be completed within 4 weeks of the first dose of study
    treatment.

    6. Patients currently receiving (or unable to stop use at least 1 week prior to
    receiving the first dose of AZD3759/AZD9291) medications or herbal supplements known
    to be potent inhibitors or inducers of cytochrome P450 3A4/5 and potential inhibitors
    of cytochrome P450 2C8 (for patients to be enrolled into AZD9291 cohorts only).

    7. 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.

    8. Known intracranial haemorrhage which is unrelated to tumour

    9. Refractory nausea and vomiting if not controlled by supportive therapy, chronic
    gastrointestinal diseases, inability to swallow the formulated product or previous
    significant bowel resection that would preclude adequate absorption of
    AZD3759/AZD9291

    10. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled
    hypertension and active bleeding diatheses

    11. Inadequate bone marrow reserve or organ function

    12. Clinically significant ECG abnormalities or any factors that increase the risk of
    corrected QT interval prolongation or risk of arrhythmic events

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Safety and Tolerability (The number of patients with each AE by system organ class, preferred term and CTCAE grade)

    Secondary Outcome Measures

    Plasma concentration of AZD3759 and metabolite and pharmacokinetics parameters after single dose of AZD3759(Cmax, tmax, terminal rate constant, half life, AUC, clearance, volume of distribution, mean residence time)

    Plasma,urine,cerebrospinal fluid concentration of AZD3759 and metabolite and pharmacokinetics parameters after multiple dosing(Cmax,ss, tmax,ss, Cmin,ss, AUCss, CLss/F).

    4b-hydroxy cholesterol in Part B patients with BM

    The effect of food on the pharmacokinetics of a single dose of AZD3759 in plasma

    Tumour response of AZD3759 and AZD9291

    Cerebrospinal fluid response rate for patients with LM and/or BM

    Changes from baseline in central nervous system symptoms (analyzed from QLQ-BN20) in patients with LM treated with AZD3759 /AZD9291

    Plasma,urine, cerebrospinal fluid concentration of AZD3759 and metabolite and pharmacokinetics parameters after multiple dosing (extent of accumulation, renal clearance, time dependency of pharmacokinetics and amount of drug excreted)

    Plasma, cerebrospinal fluid concentration of AZD9291 and metabolite and pharmacokinetics parameters after multiple dose of AZD9291(Cmax,ss, tmax,ss, Cmin,ss, AUCss, CLss/F).

    Plasma, cerebrospinal fluid concentration of AZD9291 and metabolites and pharmacokinetics parameters after multiple dosing (extent of accumulation, renal clearance, time dependency of pharmacokinetics and amount of drug excreted)

    Overall survival follow up for all expansion patients

    Trial Keywords

    Non Small Cell Lung Cancer, EGFR, Tyrosine kinase inhibitor,EGFR mutation positive, Brain Metastasis, Leptomeningeal Metastasis