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

Trial Status: Closed to Accrual

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

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

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: CLOSED_TO_ACCRUAL

California

Orange
UC Irvine Health / Chao Family Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
San Diego
University of California San Diego
Status: COMPLETED

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: COMPLETED

Indiana

Indianapolis
Indiana University / Melvin and Bren Simon Cancer Center
Status: CLOSED_TO_ACCRUAL

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: CLOSED_TO_ACCRUAL

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

South Carolina

Charleston
Medical University of South Carolina
Status: CLOSED_TO_ACCRUAL

Texas

Houston
M D Anderson Cancer Center
Status: ADMINISTRATIVELY_COMPLETE

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 Phase Phase III

Trial Type Treatment

Lead Organization
AstraZeneca Pharmaceuticals LP

  • Primary ID D5160C00003
  • Secondary IDs NCI-2014-02081
  • Clinicaltrials.gov ID NCT02151981