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A Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib

NCT03239340

Description:

A multicentre, open-label, single-arm, molecular profiling study of patients with EGFR mutation-positive locally advanced or metastatic NSCLC treated with osimertinib

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

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib
  • Official Title: A Multicentre, Open-label, Single-arm, Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib

Clinical Trial IDs

  • ORG STUDY ID: D5161C00003
  • NCT ID: NCT03239340

Conditions

  • EGFR Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
OsimertinibTAGRISSO, AZD9291Osimertinib

Purpose

A multicentre, open-label, single-arm, molecular profiling study of patients with EGFR mutation-positive locally advanced or metastatic NSCLC treated with osimertinib

Detailed Description

      Study design This is a phase II, open-label, single-arm tissue and plasma acquisition study
      assessing the efficacy, safety and underlying resistance mechanisms of osimertinib (80 mg
      orally, once daily) as first-line treatment in patients with locally advanced or metastatic
      EGFR mutation positive non-small cell lung cancer who are EGFR tyrosine kinase inhibitor
      treatment-naïve and eligible for first-line treatment. Participants with EGFR
      mutation-positive non-small cell lung cancer will be required to consent to at least 2
      mandatory tumour biopsies to be considered for enrolment in this study. The first biopsy will
      be done prior to initiating treatment with osimertinib and the second biopsy will be obtained
      any time between Investigator assessed, Response Evaluation Criteria in Solid Tumours version
      1.1 (RECIST 1.1)-defined progression and up to 7 days after the discontinuation of
      osimertinib. A third optional biopsy may be taken during the course of treatment at the
      Investigator's discretion if the patient consents and if clinically feasible. Tumour tissue
      and plasma samples will be collected and examined for genetic and non genetic aberrations
      that may be important in determining response and resistance to the treatment that
      participants will receive as a part of their cancer care. Patients should continue on
      osimertinib until progression or until other treatment discontinuation criteria are met.
      However, if patients continue to show clinical benefit to treatment as judged by the
      Investigator, patients may continue to receive osimertinib beyond RECIST 1.1-defined
      progression. Therefore, there is no maximum duration of treatment. Tumour assessments are to
      be performed at baseline and then every 8 weeks until progression. Patients will be followed
      up for a period of 28 days following discontinuation of osimertinib. Target patient
      population Male and female patients aged 18 years and over with locally advanced or
      metastatic pathologically confirmed adenocarcinoma of the lung, not amenable to curative
      surgery or radiotherapy. Patients will have a tumour that harbours one of the EGFR mutations
      known to be associated with EGFR tyrosine kinase inhibitor sensitivity, either alone or in
      combination with other EGFR mutations (EGFR mutation status determined by a local
      laboratory). Patients must be EGFR tyrosine kinase inhibitor treatment-naïve and eligible to
      receive first line treatment with osimertinib. Investigational product, dosage and mode of
      administration Osimertinib is an oral, potent, selective, irreversible inhibitor of both EGFR
      tyrosine kinase inhibitor sensitizing and resistance mutations in non-small cell lung cancer
      with a significant selectivity margin over wild type EGFR. Osimertinib (80 mg orally, once
      daily) will be administered. Doses may be reduced to 40 mg if needed.
    

Trial Arms

NameTypeDescriptionInterventions
OsimertinibExperimentalAn oral, potent, selective, irreversible inhibitor of both EGFR tyrosine kinase inhibitor sensitizing and resistance mutations in non-small cell lung cancer
  • Osimertinib

Eligibility Criteria

        Inclusion Criteria:

          1. Provision of informed consent prior

          2. Patients aged 18 years or older

          3. Patients with histological confirmation of locally advanced or metastatic NSCLC

          4. Patients with M1 stage according to the Tumor, Node and Metastasis Classification of
             Malignant Tumours (TNM)

          5. Patients with an EGFR deletion or mutation known (from tumour biopsy or plasma) to be
             associated with EGFR TKI sensitivity

          6. Existence of measurable or evaluable disease (as per RECIST 1.1 criteria).

          7. Possibility of obtaining sufficient tissue sample, via a biopsy or surgical resection
             of the primary tumour or metastatic tumour tissue

          8. WHO performance status 0-1

          9. Life expectancy ≥12 weeks

         10. Adequate coagulation: international normalised ratio (INR) ≤1.5 for patients on
             anti-coagulation therapy

         11. Capacity to swallow

         12. Patients able to complete study and within geographical proximity allowing for
             adequate follow up

         13. Resolution of all acute toxic effects of previous anticancer therapy

         14. Female patients should be using highly effective contraceptive measures, and must have
             a negative pregnancy test prior to start of dosing if of childbearing potential

         15. Male patients should be willing to use barrier contraception

        Exclusion Criteria:

          1. Locally advanced lung cancer candidate for curative treatment through radical surgery
             and/or radio(chemo)therapy

          2. Patients diagnosed with another lung cancer subtype

          3. Patients with an EGFR exon 20 insertion

          4. Patients with just one measurable or evaluable tumour lesion that has been resected or
             irradiated prior to their enrolment in the study

          5. Second active neoplasia

          6. Treatment with an investigational drug within five half-lives of the compound

          7. Participation in another clinical study with an investigational product (IP) during
             the last 3 weeks before the first day of study treatment

          8. Patients who have received prior immunotherapies

          9. Patients who have received prior EGFR treatments for lung cancer

         10. Patients who have received prior treatment with an EGFR TKI including in the adjuvant
             setting

         11. Patients who have received previous treatment for metastatic or stage IV disease

         12. Prior treatment with cytotoxic chemotherapy for advanced NSCLC

         13. Patients with a history of cancer that has been completely treated, with no evidence
             of malignant disease currently cannot be enrolled in the study if their chemotherapy
             was completed less than 6 months prior and/or have received a bone marrow transplant
             less than 2 years before the first day of study treatment

         14. 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

         15. Any evidence of severe or uncontrolled systemic diseases

         16. Patients who have had a surgical procedure unrelated to the study within 14 days or
             major surgery within 1 month prior to the administration of the study drug

         17. Past medical history of interstitial lung disease, drug-induced interstitial lung
             disease, radiation pneumonitis

         18. Any of the following cardiac criteria: Mean resting QT interval corrected for heart
             rate (QTc) more than 470 msec, obtained from 3 ECGs, using the screening clinic ECG
             machine derived QTc value. Any clinically important abnormalities in rhythm,
             conduction or morphology of resting ECG e.g. complete left bundle branch block, third
             degree heart block and second degree heart block. 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 in first degree relatives or any concomitant medication
             known to prolong the QT interval

         19. Uncontrolled, active or symptomatic metastases of CNS, carcinomatous meningitis or
             leptomeningeal disease indicated by known clinical symptoms, cerebral oedema and/or
             progressive neoplasia

         20. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to
             swallow the formulated product or previous significant bowel resection that would
             preclude adequate absorption of osimertinib

         21. Inadequate bone marrow reserve or organ function

         22. Female patients who are breastfeeding

         23. Patients currently receiving medications or herbal supplements known to be potent
             inducers of cytochrome P450

         24. Patient unwilling to undergo a biopsy at the time of disease progression

         25. History of hypersensitivity to active or inactive excipients of osimertinib or drugs
             with a similar chemical structure or class to osimertinib

         26. Judgment by the Investigator that the patient should not participate in the study if
             the patient is unlikely to comply with study procedures, restrictions and requirements

         27. Involvement in the planning and/or conduct of the study

         28. Previous enrolment in the present study Prior chemotherapy may affect the resistance
             profile under study; however, patients who have received prior chemotherapy may be
             permitted if the patients have not received more than 4 cycles of first-line
             chemotherapy with a limit of 20% of the total enrolment.
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of patients with a given genetic and proteomic marker at the point of disease progression as defined by the Investigator
Time Frame:Genetic and Proteomic markers will be assessed from tissue samples collected prior to initiation of treatment and at the time of disease progression for up to 4 years
Safety Issue:
Description:To examine the genetic and proteomic profile at the point of disease progression in patients receiving osimertinib as first-line EGFR tyrosine kinase inhibitor therapy for EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer compared to the profile prior to initiation of treatment

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:At baseline and every 8 weeks from enrolment until disease progression or death or end of study for up to 4 years
Safety Issue:
Description:PFS is defined as the time from first dose of osimertinib until the date of RECIST 1.1-defined progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to progression.
Measure:Objective Response Rate (ORR)
Time Frame:At baseline and every 8 weeks from enrolment until disease progression or death or end of study up to 4 years
Safety Issue:
Description:ORR is defined as the number (%) of patients with at least one visit response of complete response or partial response that is confirmed at least 4 weeks later.
Measure:Duration of Response (DoR)
Time Frame:At baseline and every 8 weeks from enrolment until disease progression of death or end of study up to 4 years
Safety Issue:
Description:DoR is defined as the time from the date of first documented response, (that is subsequently confirmed) until date of documented progression or death in the absence of disease progression, the end of response should coincide with the date of progression or death from any cause used for the PFS endpoint.
Measure:Time to Treatment Discontinuation or Death (TTD)
Time Frame:At every visit from enrolment to end of treatment or death or end of study up to 4 years
Safety Issue:
Description:TTD is defined as the time from the date of first dose of osimertinib to the earliest of treatment discontinuation or death.
Measure:Time to first subsequent therapy or Death (TFST)
Time Frame:At every visit from enrolment to start of first subsequent therapy or death or end of study up to 4 years
Safety Issue:
Description:TFST is defined as the time from the date of first dose of osimertinib to the earlier of the date of anticancer therapy start date following study treatment discontinuation, or death.
Measure:Tumour shrinkage/ depth of response
Time Frame:At baseline and every 8 weeks from enrolment until disease progression or death or end of study up to 4 years
Safety Issue:
Description:Tumour shrinkage is defined as the best change from baseline in the sum of diameters of target lesions

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • EGFR, NSCLC, Lung Cancer, Biopsy, Molecular Profiling

Last Updated

October 9, 2017