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A Study of Osimertinib With or Without Chemotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer

NCT04351555

Description:

This is a Phase III, randomised, controlled, multi-centre, 3-arm study of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy, versus SoC chemotherapy alone, for the treatment of patients with EGFRm (Ex19del and/or L858R), resectable Non-Small Cell Lung Cancer

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

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Osimertinib With or Without Chemotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer
  • Official Title: A Phase III, Randomised, Controlled, Multi-center, 3-Arm Study of Neoadjuvant Osimertinib as Monotherapy or in Combination With Chemotherapy Versus Standard of Care Chemotherapy Alone for the Treatment of Patients With Epidermal Growth Factor Receptor Mutation Positive, Resectable Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: D516AC00001
  • NCT ID: NCT04351555

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
OsimertinibAZD9291; TAGRISSOOsimertinib monotherapy
CisplatinOsimertinib with platinum-based chemotherapy
CarboplatinOsimertinib with platinum-based chemotherapy
PlaceboPlacebo with platinum-based chemotherapy
PemetrexedOsimertinib with platinum-based chemotherapy

Purpose

This is a Phase III, randomised, controlled, multi-centre, 3-arm study of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy, versus SoC chemotherapy alone, for the treatment of patients with EGFRm (Ex19del and/or L858R), resectable Non-Small Cell Lung Cancer

Trial Arms

NameTypeDescriptionInterventions
Osimertinib with platinum-based chemotherapyExperimentalOsimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator) plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin)
  • Osimertinib
  • Cisplatin
  • Carboplatin
  • Pemetrexed
Placebo with platinum-based chemotherapyPlacebo ComparatorPlacebo plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin)
  • Cisplatin
  • Carboplatin
  • Placebo
  • Pemetrexed
Osimertinib monotherapyExperimentalOsimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator)
  • Osimertinib

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female, at least 18 years of age. For patients aged <20 years and enrolled in
             Japan, a written informed consent should be obtained from the patient and his or her
             legally acceptable representative

          -  Histologically or cytologically documented NSCLC with completely resectable (Stage II
             - IIIB N2) disease (according to Version 8 of the IASLC Cancer Staging Manual [IASLC
             Staging Manual in Thoracic Oncology 2016]).

          -  Complete surgical resection of the primary NSCLC must be deemed achievable, as
             assessed by a MDT evaluation (which should include a thoracic surgeon, specialised in
             oncologic procedures).

          -  Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 at enrolment, with no
             deterioration over the previous 2 weeks prior to baseline or day of first dosing

          -  A tumour which harbours one of the 2 common EGFR mutations known to be associated with
             EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR
             mutations (ie, T790M, G719X, Exon20 insertions, S7681 and L861Q).

        Exclusion Criteria:

          -  Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required
             steroid treatment, or any evidence of clinically active ILD.

          -  History of another primary malignancy, except for the following: Malignancy treated
             with curative intent and with no known active disease ≥2 years before the first dose
             of investigational product (IP) and of low potential risk for recurrence; Adequately
             treated non-melanoma skin cancer or lentigo malignancy without evidence of disease;
             Adequately treated carcinoma in situ without evidence of disease

          -  Patients who have pre-operative radiotherapy treatment as part of their care plan

          -  Mixed small cell and NSCLC histology

          -  Stages I, IIIB N3, IIIC, IVA, and IVB NSCLC

          -  T4 tumours infiltrating the aorta, the oesophagus and/or the heart; and/or any bulky
             N2 disease

          -  Patients who are candidates to undergo only segmentectomies or wedge resections

          -  Prior treatment with any systemic anti-cancer therapy for NSCLC including
             chemotherapy, biologic therapy, immunotherapy, or any investigational drug

          -  Prior treatment with EGFR-TKI therapy

          -  Current use of (or unable to stop use prior to receiving the first dose of study
             treatment) medications or herbal supplements known to be strong inducers of cytochrome
             P450 (CYP) 3A4 (at least 3 weeks prior)
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Major Pathological Response (MPR)
Time Frame:From date of randomization to an average of 12 weeks after the first dose
Safety Issue:
Description:Defined as ≤10% residual cancer cells in the surgical specimen, as assessed per central pathology laboratory post-surgery

Secondary Outcome Measures

Measure:Pathological complete response (pCR)
Time Frame:From date of randomization to an average of 12 weeks after the first dose
Safety Issue:
Description:Defined as absence of any residual cancer cells in the surgical specimen assessed post-surgery
Measure:Event-free survival (EFS)
Time Frame:Up to approximately 21 months after the last patient is randomized
Safety Issue:
Description:An event is defined as documented disease progression that precludes surgery or requires non-protocol therapy; recurrence or a new lesion, local or distant (a new primary malignancy confirmed by pathology is not considered to be an EFS event.); death due to any cause
Measure:Overall Survival (OS)
Time Frame:Up to approximately 5.5 years after the last patient is randomized
Safety Issue:
Description:Patients will be followed up to approximately 5.5 years after they are randomized.
Measure:Disease free survival (DFS)
Time Frame:From date of randomization up to approximately 15 months after date of resection
Safety Issue:
Description:DFS is defined as the time from the date of surgery until the first date of disease recurrence (local or distant) or date of death due to any cause, whichever occurs first. If there is residual disease after surgery (eg. positive margins), the DFS event is the date of surgery.
Measure:Downstaging
Time Frame:From date of randomization to an average of 12 weeks after the first dose
Safety Issue:
Description:Measured using lymph node staging
Measure:Difference between treatment arms in change from baseline in EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items)
Time Frame:From randomization to 24 weeks post-surgery
Safety Issue:
Description:Assess disease-related symptoms, functioning, and global health status/quality-of-life in patients
Measure:Concordance of EGFRm status between tumour tissue DNA and patient-matched plasma-derived ctDNA
Time Frame:Baseline
Safety Issue:
Description:
Measure:Corcordance of EGFR mutation status between the local and central cobas EGFR mutation test results from baseline tumour samples
Time Frame:Baseline
Safety Issue:
Description:
Measure:PK plasma concentrations of osimertinib
Time Frame:From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Difference between treatment arms in change from baseline in EORTC QLQ-LC13 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 items)
Time Frame:From randomization to 24 weeks post-surgery
Safety Issue:
Description:Assess lung cancer-associated symptoms and side effects from conventional chemotherapy and radiotherapy

Details

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

Trial Keywords

  • Resectable; Non-Small Cell Lung Cancer; Osimertinib; EGFRm Positive; Neoadjuvant

Last Updated

April 15, 2020