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

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

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

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Cisplatin; Drug: Osimertinib; Drug: Pemetrexed

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hong Yang, Ph.D.,M.D.; Phone Number: 13560405144 13560405144; Email: yanghong@sysucc.org.cn
• Study Contact Backup: Name: Jiyang Chen, Ph.D.,M.D.; Phone Number: 008618826238208; Email: chenjy1@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-Sen University Cancer Center
      • Contact: Hong Yang, Ph.D.,M.D.; Phone Number: 008613560405144; Email: yanghong@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Cisplatin; Cisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 2 cycles.; Other Names: DDP; Drug: Osimertinib; 80mg/qd oral for 60 days; Other Names: AZD9291; TAGRISSO; Drug: Pemetrexed; Pemetrexed (500 mg/m2) to be administered with cisplatin on Day 1 of every 3-week cycle for 2 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete lymph node clearance rate	the ratio of ypN0 percentage after resection	From date of enrollment to an average of 12 weeks after the first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response (MPR)	Defined as ≤10% residual cancer cells in the main tumour, as assessed per central pathology laboratory post-surgery	From date of enrollment to an average of 12 weeks after the first dose
Pathological complete response (pCR)	Defined as absence of any residual cancer cells in the dissected tumour samples, including the main tumour and lymph nodes, assessed post-surgery	From date of enrollment to an average of 12 weeks after the first dose
Downstaging	Measured using pathologic mediastinal lymph node evaluation	From date of enrollment to an average of 12 weeks after the first dose
Disease free survival (DFS)	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.	From date of enrollment up to approximately 42 months after date of resection

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Hong Yang, Ph.D.,M.D., Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2021
• Primary Completion (Actual): September 1, 2023
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: August 15, 2021
• First Submitted That Met QC Criteria: August 15, 2021
• First Posted (Actual): August 18, 2021

Study Record Updates

• Last Update Posted (Estimated): January 15, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: neoadjuvant; Non small cell lung cancer; EGFR-TKI
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Folic Acid Antagonists; Osimertinib; Pemetrexed
• Other Study ID Numbers: SYSUCC B2021-167-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No