Clinical Trials /

AZD9291 (Osimertinib) Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer

NCT02151981

Description:

A Phase III, Open Label, Randomized Study of Osimertinib versus Platinum-Based Doublet Chemotherapy for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours harbour a T790M mutation within the Epidermal Growth Factor Receptor Gene

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

Active, not recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT02151981

Trial Eligibility

Document

Title

  • Brief Title: AZD9291 (Osimertinib) Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer
  • Official Title: A Phase III, Open Label, Randomized Study of AZD9291 Versus Platinum-Based Doublet Chemotherapy for Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Whose Disease Has Progressed With Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Whose Tumours Harbour a T790M Mutation Within the Epidermal Growth Factor Receptor Gene (AURA3).

Clinical Trial IDs

  • ORG STUDY ID: D5160C00003
  • NCT ID: NCT02151981

Conditions

  • Anticancer Treatment

Interventions

DrugSynonymsArms
ChemotherapyOsimertinib, Platinum-based Doublet-ChemotherapyOsimertinib
Cross-over to OsimertinibOsimertinib

Purpose

A Phase III, Open Label, Randomized Study of Osimertinib versus Platinum-Based Doublet Chemotherapy for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours harbour a T790M mutation within the Epidermal Growth Factor Receptor Gene

Detailed Description

      This is a phase III, open label, randomized study assessing Osimertinib (80 mg, orally, once
      daily) versus platinum-based doublet chemotherapy (standard of care) in subjects with
      confirmed diagnosis of Epidermal Growth Factor Receptor (EGFR) mutation positive NSCLC, who
      have progressed following prior therapy with an approved Epidermal Growth Factor Receptor
      Tyrosine Kinase Inhibitor (EGFR-TKI) agent and whose tumours harbour a T790M mutation within
      the EGFR Gene. Subjects must be chemotherapy naive and must agree to provide a biopsy for
      central confirmation of T790 mutation status following confirmed disease progression on their
      first line EGFR-TKI treatment (e.g. erlotinib, gefitinib or afatinib). Suitable subjects will
      then be randomized to receive either Osimertinib (80mg orally, once daily) or platinum-based
      doublet chemotherapy (pemetrexed 500 mg/m2 + carboplatin area under the plasma
      concentration-time curve AUC 5 or pemetrexed 500 mg/m2 + cisplatin 75 mg/m2) on Day 1 of
      every 21-day cycle in a 2:1 (Osimertinib: platinum-based doublet chemotherapy) ratio. Once
      subjects on the platinum-based doublet chemotherapy arm are determined to have objective
      radiological progression according to RECIST 1.1 by the investigator and confirmed by
      independent central imaging review, they will be given the opportunity to begin treatment
      with Osimertinib 80mg, once daily. These subjects may continue treatment with Osimertinib
      even after disease progression, as long as they are continuing to show clinical benefit, as
      judged by the investigator. The primary objective of the study is to assess the efficacy of
      Osimertinib compared with platinum-based doublet chemotherapy by assessment of Progression
      Free Survival (PFS), using investigator assessments according to Response Evaluation Criteria
      in Solid Tumours (RECIST 1.1), as well as asensitivity analysis of Progression Free Survival
      using Blinded Independent Central Review (BICR).

Trial Arms

NameTypeDescriptionInterventions
OsimertinibExperimentalOsimertinib 80 mg, orally, once daily
  • Chemotherapy
  • Cross-over to Osimertinib
Platinum-based doublet chemotherapyActive Comparatorpemetrexed 500mg/m2 + carboplatin AUC5 or pemetrexed 500mg/m2 + cisplatin 75mg/m2
  • Chemotherapy

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects with histologically or cytologically documented NSCLC.

          -  Locally advanced or metastatic NSCLC

          -  Radiological documentation of disease progression following 1st line EGFR TKI
             Treatment without any further treatment

          -  Eligible to receive treatment with the selected doublet-chemotherapy

          -  Central confirmation of T790M+ mutation status

          -  World Health Organization (WHO) performance status 0-1

          -  At least one lesion, not previously irradiated.

        Exclusion Criteria:

          -  • Prior neo-adjuvant or adjuvant chemotherapy treatment within 6 months prior of
             starting 1st EGFR TKI treatment

          -  Treatment with more than one prior line of treatment for advanced NSCLC

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

          -  Any investigational agents or other anticancer drugs from a previous treatment regimen
             or clinical study within 14 days of the first dose of study treatment

          -  Previous treatment with Osimertinib, or a 3rd generation EGFR TKI

        For subjects who cross-over to Osimertinib:

          -  Once subjects on the platinum-based doublet chemotherapy arm are determined to have
             objective radiological progression according to RECIST 1.1 by the investigator and
             confirmed by independent central imaging review.

          -  At least 14 days since last dose of platinum-based doublet chemotherapy
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS) by Investigator Assessment
Time Frame:RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Safety Issue:
Description:Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of randomisation until the date of PD (by investigator assessment) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR) by Investigator Assessment
Time Frame:RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Safety Issue:
Description:Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR prior to progression or any further therapy.
Measure:Duration of Response (DoR) by Investigator Assessment
Time Frame:RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Safety Issue:
Description:Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. DoR is the time from the date of first documented response until the date of documented progression or death in the absence of disease progression.
Measure:Disease Control Rate (DCR) by Investigator Assessment
Time Frame:RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Safety Issue:
Description:Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. DCR is the percentage of patients with best response of CR, PR or SD at >=6 weeks, prior to any progressive disease (PD).
Measure:Tumour Shrinkage by Investigator Assessment
Time Frame:RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Safety Issue:
Description:Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Tumour size was calculated as the sum of the longest diameters (SLD) of the Target Lesions. Tumour shrinkage is percentage change in tumour size from baseline using RECIST v1.1 tumour response.
Measure:Secondary: Overall Survival (OS)
Time Frame:From date of randomization until time of final OS analysis, a median follow-up of 43 months
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Advanced Non-Small Cell Lung Cancer; T790M Mutation Positive

Last Updated

August 4, 2021