NOCE01: Neoadjuvant Osimertinib + Chemotherapy for EGFR-mutant Stage III NSCLC

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05011487

Collaborator

(none)

Enrollment

Location

Arm

84.6

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase II, single-arm, multi-center study of neoadjuvant osimertinib in combination with chemotherapy for the treatment of patients with resectable EGFR-mutant stage III (N2) non-squamous non-small cell lung cancer

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: Osimertinib Drug: Cisplatin Drug: Pemetrexed	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

osimertinib plus chemotherapyosimertinib plus chemotherapy

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Neoadjuvant Osimertinib Plus Chemotherapy for EGFR-mutant Stage III N2 Non-squamous Non-small Cell Lung Cancer

Actual Study Start Date :

Aug 13, 2021

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Sep 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: osimertinib plus chemotherapy Osimertinib (80mg/qd) po. for 60 days with two cycles of Pemetrexed (500 mg/m2) to be administered with cisplatin (75mg/m2) on Day 1 of every 3-week cycle for 2 cycles	Drug: Osimertinib 80mg/qd oral for 60 days Other Names: AZD9291 TAGRISSO Drug: Cisplatin Cisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 2 cycles. Other Names: DDP Drug: Pemetrexed Pemetrexed (500 mg/m2) to be administered with cisplatin on Day 1 of every 3-week cycle for 2 cycles

Arm

Intervention/Treatment

Experimental: osimertinib plus chemotherapy

Osimertinib (80mg/qd) po. for 60 days with two cycles of Pemetrexed (500 mg/m2) to be administered with cisplatin (75mg/m2) on Day 1 of every 3-week cycle for 2 cycles

Drug: Osimertinib

80mg/qd oral for 60 days

Other Names:

AZD9291

TAGRISSO

Drug: Cisplatin

Cisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 2 cycles.

Other Names:

DDP

Drug: Pemetrexed

Pemetrexed (500 mg/m2) to be administered with cisplatin on Day 1 of every 3-week cycle for 2 cycles

Outcome Measures

Primary Outcome Measures

complete lymph node clearance rate [From date of enrollment to an average of 12 weeks after the first dose]
the ratio of ypN0 percentage after resection

Secondary Outcome Measures

Major Pathological Response (MPR) [From date of enrollment 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
Pathological complete response (pCR) [From date of enrollment to an average of 12 weeks after the first dose]
Defined as absence of any residual cancer cells in the dissected tumour samples, including the main tumour and lymph nodes, assessed post-surgery
Downstaging [From date of enrollment to an average of 12 weeks after the first dose]
Measured using pathologic mediastinal lymph node evaluation
Disease free survival (DFS) [From date of enrollment up to approximately 42 months after date of resection]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically documented N2 positive non-squamous NSCLC with resectable (Stage IIIA or T3-4N2 IIIB) 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, specialized 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
T4 tumours infiltrating the aorta, the oesophagus and/or the heart; and/or any bulky N2 disease deemed unresectable
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)