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
Phase 3
Active, not recruiting
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT04351555
- Lead Sponsor
- AstraZeneca
- Brief Summary
This is a Phase III, randomised, controlled, 3-arm, multi-centre study of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy, versus SoC chemotherapy alone, for the treatment of patients with resectable EGFRm Non-Small Cell Lung Cancer
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 358
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 non-squamous 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 (eg., 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 (including any known or suspected synchronous primary lung cancer), 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; Any synchronous Stage IA primary lung cancer that is ≤2 cm and planned to be resected during surgery for the Stage II to IIIB N2 lung tumour.
- 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 great vessels, the carina, the trachea, the oesophagus, the heart, and/or the vertebral body; 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: Placebo with platinum-based chemotherapy Placebo Placebo plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin) Arm 1: Placebo with platinum-based chemotherapy Carboplatin Placebo plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin) Arm 2: Osimertinib with platinum-based chemotherapy Carboplatin Osimertinib 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) Arm 3: Osimertinib monotherapy Osimertinib Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator) Arm 1: Placebo with platinum-based chemotherapy Cisplatin Placebo plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin) Arm 2: Osimertinib with platinum-based chemotherapy Cisplatin Osimertinib 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) Arm 1: Placebo with platinum-based chemotherapy Pemetrexed Placebo plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin) Arm 2: Osimertinib with platinum-based chemotherapy Osimertinib Osimertinib 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) Arm 2: Osimertinib with platinum-based chemotherapy Pemetrexed Osimertinib 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)
- Primary Outcome Measures
Name Time Method Major Pathological Response (MPR) From date of randomization to an average of 12 weeks after the first dose Defined as ≤10% residual cancer cells in the main tumour, as assessed per central pathology laboratory post-surgery
- Secondary Outcome Measures
Name Time Method 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) From date of randomization up to approximately 5.5 years after the last patient is randomized Assess disease-related symptoms, functioning, and global health status/quality-of-life in patients
PK plasma concentrations of osimertinib From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days) Event-free survival (EFS) From date of randomization up to approximately 5.5 years after the last patient is randomized An event is defined as documented disease progression that precludes surgery or prevents completion of definitive surgery; recurrence or a new lesion, local or distant (a new primary malignancy, confirmed by pathology if clinically feasible, is not considered to be an EFS event); death due to any cause
Concordance of EGFRm status between tumour tissue DNA and patient-matched plasma-derived ctDNA Baseline 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) From date of randomization up to approximately 5.5 years after the last patient is randomized Assess lung cancer-associated symptoms and side effects from conventional chemotherapy and radiotherapy
Corcordance of EGFR mutation status between the local and central cobas EGFR mutation test results from baseline tumour samples Baseline Overall Survival (OS) From date of randomization up to approximately 5.5 years after the last patient is randomized OS will be defined as the time from the date of randomisation until death due to any cause
Pathological complete response (pCR) From date of randomization to an average of 12 weeks after the first dose Defined as absence of any viable cancer cells in the dissected tumour samples, including the main tumour, lymph nodes, and margins as assessed per central pathology laboratory post-surgery
Disease free survival (DFS) From date of randomization up to approximately 5.5 years after the last patient is randomized 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.
Downstaging From date of randomization to an average of 12 weeks after the first dose Measured using pathologic mediastinal lymph node evaluation
Trial Locations
- Locations (1)
Research Site
🇻🇳Ho Chi Minh, Vietnam