Clinical Trials /

AZD9291, an Irreversible EGFR-TKI, in Relapsed EGFR-mutated Non-small Cell Lung Cancer Patients Previously Treated With an EGFR-TKI, Coupled to Extensive Translational Studies

NCT02504346

Description:

Phase II, single-arm study to assess the safety and efficacy of AZD9291 (80 mg, orally, once daily) in second-line (or later) patients with EGFR mutation-positive, locally advanced or metastatic NSCLC, who have progressed following treatment with an approved epidermal growth factor tyrosine kinase inhibitor agent.

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

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: AZD9291, an Irreversible EGFR-TKI, in Relapsed EGFR-mutated Non-small Cell Lung Cancer Patients Previously Treated With an EGFR-TKI, Coupled to Extensive Translational Studies
  • Official Title: AZD9291, an Irreversible EGFR-TKI, in Relapsed EGFR-mutated Non-small Cell Lung Cancer Patients Previously Treated With an EGFR-TKI, Coupled to Extensive Translational Studies

Clinical Trial IDs

  • ORG STUDY ID: 2015/10301
  • NCT ID: NCT02504346

Conditions

  • Lung Cancer
  • Targeted Therapy

Interventions

DrugSynonymsArms
AZD9291Treatment

Purpose

Phase II, single-arm study to assess the safety and efficacy of AZD9291 (80 mg, orally, once daily) in second-line (or later) patients with EGFR mutation-positive, locally advanced or metastatic NSCLC, who have progressed following treatment with an approved epidermal growth factor tyrosine kinase inhibitor agent.

Detailed Description

      This is a phase II, single-arm study to assess the safety and efficacy of AZD9291 (80 mg,
      orally, once daily) in second-line (or later) patients with EGFR mutation-positive, locally
      advanced or metastatic NSCLC, who have progressed following treatment with an approved
      epidermal growth factor tyrosine kinase inhibitor agent.

      If feasible, subjects will have to provide a biopsy sample for molecular testing following
      confirmed disease progression on the most recent treatment regimen. A second biopsy will be
      sampled at progression on AZD9291, if feasible. Liquid biopsies will be sampled throughout
      the treatment period.

      Subjects should continue on study treatment until RECIST 1.1-defined progression or until a
      treatment discontinuation criterion is met. There is no maximum duration of treatment as
      subjects may continue to receive investigational product beyond RECIST 1.1 defined
      progression as long as they are continuing to show clinical benefit, as judged by the
      investigator.
    

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalNon-randomized trial, all patients receive therapy - singel-arm
  • AZD9291

Eligibility Criteria

        Inclusion Criteria:

          1. Provision of signed and dated, written informed consent.

          2. Age > 18 years.

          3. Histologically or cytologically documented locally advanced or metastatic NSCLC not
             amenable to curative surgery or radiotherapy.

          4. Radiological disease progression following at least one prior EGFR TKI.

          5. Documented EGFR mutation known to be associated with EGFR TKI sensitivity (also
             including T790M).

          6. ECOG status 0-2 and a minimum life expectancy of 12 weeks.

          7. At least one lesion, not previously irradiated and not chosen for biopsy during the
             study screening period, that can be accurately measured at baseline according to
             RECIST 1.1.

          8. Females should be using 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 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 postmenopausal if they have been
                  amenorrheic for 12 months or more following cessation of exogenous hormonal
                  treatments and with Luteinizing 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.

          9. Male subjects must be willing to use barrier contraception.

        Exclusion Criteria:

          -  1. Treatment with an EGFR-TKI within 8 days or approximately 5x half-life, whichever
             is the longer, of the first dose of study treatment.

             2. Treatment with cytotoxic chemotherapy, investigational agents or other anticancer
             drugs from a previous treatment regimen or clinical study within 14 days or
             approximately 5x half-life, whichever is the longer, of the first dose of study
             treatment.

             3. Previous treatment with AZD9291, or another EGFR TKI with similar profile, e.g.
             CO-1686 4. Major surgery within 4 weeks of inclusion 5. Radiotherapy treatment to more
             than 30% of the bone marrow or with a wide field of radiation within 4 weeks of
             inclusion 6. Subjects currently receiving (or unable to stop using) potent inhibitors
             or inducers of CYP3A4 7. Any unresolved toxicities from prior therapy greater than
             CTCAE grade 1 (with the exception of alopecia grade 2) at the time of starting study
             treatment.

             8. Spinal cord compression or brain metastases unless asymptomatic and on stable
             steroid dosage for at least 2 weeks prior to start of study treatment.

             9. Any evidence of severe or uncontrolled systemic diseases which in the
             investigator's opinion makes it undesirable for the subject to participate in the
             trial or which would jeopardise compliance with the protocol, or active infection
             including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening
             for chronic conditions is not required.

             10. Gastrointestinal conditions incompatible with swallowing or precluding absorption
             of AZD9291.

             11. Exclude based on any of the following cardiac criteria:

          -  Mean resting corrected QT interval (QTc using Fredericia's formula) > 470 msec

          -  Any clinically important abnormalities in rhythm, conduction or morphology of resting
             ECG (e.g., complete left bundle branch block, third degree heart block, second degree
             heart block)

          -  Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
             such as heart failure, hypokalemia, congenital long QT syndrome, family history of
             long QT syndrome or unexplained sudden death under 40 years of age in first degree
             relatives or any concomitant medication known to prolong the QT interval 12. Current
             or previous significant interstitial lung disease or radiation pneumonitis 13.
             Absolute neutrophil count < 1.5 x 109/L 14. Platelet count < 100 x 109/L 15.
             Haemoglobin < 80 g/L 16. Alanine aminotransferase (ALT) > 2.5 times the upper limit of
             normal (ULN) if no demonstrable liver metastases or > 5 times ULN in the presence of
             liver metastases 17. Aspartate aminotransferase (AST) > 2.5 times ULN if no
             demonstrable liver metastases or > 5 times ULN in the presence of liver metastases 18.
             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 19. Creatinine >1.5 times ULN concurrent with creatinine clearance < 50
             ml/min (measured or calculated by Cockcroft and Gault equation), 20. History of
             hypersensitivity of AZD9291 (or drugs with a similar chemical structure or class.

             21. Women who are pregnant or breast-feeding, or have a positive (urine or serum)
             pregnancy test prior to study entry 22. Judgment by the investigator that the subject
             should not participate in the study if the subject is unlikely to comply with study
             procedures, restrictions and requirements.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate
Time Frame:12 weeks
Safety Issue:
Description:Measured by RECIST 1.1

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Oslo University Hospital

Last Updated

June 22, 2017