Adjuvant Treatment Based on MRD for EGFR Mutant NSCLC

NCT05536505 | Recruiting Phase 2

• 1 other identifier: CTONG2105
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 16

Brief Summary

A prospective, multicenter clinical study designed to explore the efficacy of postoperative adjuvant EGFR-TKIs therapy based on MRD status in patients with stage IB-IIIB EGFR-mutant non-squamous non-small cell lung cancer (non-squamous NSCLC). Primary endpoints include 3-year Disease-Free Survival rate (3y-DFS) and median disease-free survival (mDFS).

Conditions

MRD

Keywords

NSCLC; Adjuvant; EGFR mutation

Outcome Measures

Primary Outcomes (2)

• Disease Free Survival

  Disease free survival (DFS)- defined as the time from operation to the first documented disease progression or death, whichever occurs first.

  From date of opeartion until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• 3 yeas DFS rate

  To compare 3y-DFS rates between the two arms

  From date of opeartion until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcomes (1)

• Overall survival

  OS is defined as the time from opeartion to death, regardless of disease recurrence, assessed up to 100 months

Study Arms (2)

MRD Positivity Post Operation

EXPERIMENTAL

If MRD confirmed Positivity at either of the two timepoints (Time point 1: blood draw from the 3rd day to 7th day post operation. Time point 2: blood draw on the 28th day post operation), patients would receive icotinib until MRD turned Negativity. During MRD monitoring, icotinib would rechallenge

Genetic: Adjuvant treatment for MRD positivity

MRD Negativity Post Operation

NO INTERVENTION

If MRD confirmed negativity at both of the two timepoints (Time point 1: blood draw from the 3rd day to 7th day post operation. Time point 2: blood draw on the 28th day post operation), patients would receive ctDNA MRD monitoring.

Interventions

Adjuvant treatment for MRD positivity GENETIC

The MRD positive group would receive icotinib as adjuvant treatment. When the peripheral blood MRD turned negative, the subjects entered the drug withdrawal observation period. When the MRD turned positive again, the subjects resumed icotinib treatment. If EGFR T790M mutation was found, researchers would resume medication and choose osimertinib therapy.

MRD Positivity Post Operation

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent provided.
• Males or females aged ≥18 years, \< 80 years.
• Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.
• Target population is completely resected pathological stage IB-IIIB NSCLC with EGFR exon 19 deletions, L861Q mutation, G719X mutation and exon 21 L858R activating mutation.
• Patients who have recovered from R0 resection including lobectomy, sleeve surgery and pneumonectomy.
• ECOG performance status 0-1.
• Life expectancy ≥12 weeks.
• Adequate hematological function: Absolute neutrophil count (ANC) ≥1.8 x 109/L, and Platelet count ≥100 x 109/L, and Hemoglobin ≥9 g/dL (may be transfused to maintain or exceed this level).
• Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN in subjects without liver metastases; ≤ 5 x ULN in subjects with liver metastases.
• Adequate renal function: Serum creatinine ≤ 1.25 x ULN, or ≥ 60 ml/min.
• Female subjects should not be pregnant or breast-feeding.

You may not qualify if:

• Known severe hypersensitivity to icotinib, osimertinib or any of the excipients of this product.
• Inability to comply with protocol or study procedures.
• A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study.
• A serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease.
• Interstitial pneumonia.
• Patients with prior exposure to agents directed at the HER axis (e.g. erlotinib, gefitinib, icotinib, cetuximab, trastuzumab).
• Patients with prior chemotherapy or therapy with systemic anti-tumour therapy (e.g. monoclonal antibody therapy).
• Patients with prior radiotherapy to primary lesion or lymph nodes.
• History of another malignancy in the last 5 years with the exception of the following: Other malignancies cured by surgery alone and having a continuous disease-free interval of 5 years are permitted. Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix are permitted.
• Any unstable systemic disease (including active infection, uncontrolled hypertension (systolic pressure \> 160mmHg, diastolic pressure \> 100mmHg), unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).
• Eye inflammation or eye infection not fully treated or conditions predisposing the subject to this.
• Evidence of any other disease, neurological or metabolic dysfunction, physical examination or laboratory finding giving reasonable suspicion of a disease or condition that contraindicated the use of an investigational drug or puts the subject at high risk for treatment-related complications.
• Patient who has active serious infection (e.g. pyrexia of or 38.0℃ over) Patients who harboring exon 20 T790M mutation, EGFR 20 insertions, ALK fusion, BRAF V600E mutation, MET amplification and KRAS mutation.

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead

Study Sites (16)

Beijing Friendship Hospital, Capital Medical University

Beijing, China

NOT YET RECRUITING

Chongqing University Three Gorges Hospital

Chongqing, China

NOT YET RECRUITING

The First People's Hospital of Foshan

Foshan, China

NOT YET RECRUITING

Fujian Medical University Union Hospital

Fuzhou, China

NOT YET RECRUITING

Affiliated Cancer Hospital of Guangzhou Medical University

Guangzhou, China

NOT YET RECRUITING

Nanfang Hospital Southern Medical University

Guangzhou, China

NOT YET RECRUITING

Guangdong Provincial People's Hospital

Guanzhou, China

RECRUITING

The Second Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, China

NOT YET RECRUITING

The First Affiliated Hospital of USTC Anhui Provincial Hospital

Hefei, China

NOT YET RECRUITING

The Affiliated Hospital of Inner Mongolia Hospital

Hohhot, China

NOT YET RECRUITING

The Affiliated Hospital of Qingdao University

Qingdao, China

NOT YET RECRUITING

Zhongshan Hospital Fudan University

Shanghai, China

NOT YET RECRUITING

Shenzhen People's Hospital

Shenzhen, China

NOT YET RECRUITING

Tongji Hospital Tongji College of HUST

Wuhan, China

NOT YET RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, China

NOT YET RECRUITING

Zhongshan City People's Hospital

Zhongshan, China

NOT YET RECRUITING

Central Study Contacts

Yi-Long Wu, MD

CONTACT

020-83827812; syylwu@live.cn

Ri-Qiang Liao

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2022
• First Posted: September 13, 2022
• Study Start: September 13, 2022
• Primary Completion: October 1, 2025
• Study Completion (Estimated): October 1, 2030
• Last Updated: September 14, 2022

Record last verified: 2022-09

Locations

CN (16)