Brief Title
ctDNA-MRD Based Adjuvant Targeted Therapy for EGFR Positive Stage I Lung Adenocarcinomas
Official Title
Circulating Tumor DNA (ctDNA)-Minimal Residual Disease (MRD) Based Adjuvant Targeted Therapy in EGFR Mutation-positive Stage I Lung Adenocarcinoma Patients After Complete Surgical Resection
Brief Summary
The purpose of this study is to determine the feasibility and effectiveness of ctDNA-MRD
based adjuvant furmonertinib therapy in EGFR mutation-positive stage I lung adenocarcinoma
patients after complete surgical resection.
Detailed Description
Despite surgery provides the best chance for the cure of early-stage lung cancer patients,
20%-40% of stage I non-small cell lung cancer (NSCLC) patients still suffer from disease
relapse after R0 resection. One of the important strategies to improve survival is adjuvant
therapy.
The adjuvant chemotherapies are reported to improve outcomes of patients with stage II and
III lung cancer. However, for stage IA patients, adjuvant chemotherapy is not recommended,
while its application in stage IB patients is still controversial. The adjuvant targeted
therapy has shown promising effectiveness which can lead to better RFS of EGFR
mutation-positive stage IB-IIIA NSCLC patients than chemotherapy in according to several
phase III studies. According to the ADAURA study, stage IB NSCLC patients can benefit from
the third-generation EGFR-TKI. However, no available study has evaluated the effectiveness of
adjuvant targeted therapy in the overall cohort of stage I patients.
Molecular residual disease or minimal residual disease (MRD) refers to residual tumor cells
or relative biomarkers that persist in the body after treatment and is below the conventional
detection limit. Several studies have confirmed that positive MRD was associated with a poor
prognosis. The use of circulating tumor DNA (ctDNA) to reflect MRD at the molecular level can
overcome the shortcomings of conventional tests or radiological tests in the detection of
recurrence. ctDNA has been proven to detect MRD effectively in stage I-III lung cancer
patients and identifying MRD after surgery could facilitate the selection of patients for
customized adjuvant therapies.
Thus, the investigators innovatively propose this study to assess the effectiveness of
adjuvant targeted therapy (furmonertinib, one third-generation EGFR-TKI) in stage I lung
adenocarcinoma patients and explore the role of ctDNA as an MRD monitoring marker in guiding
personalized adjuvant therapies.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Clearance of ctDNA at 6 months
Secondary Outcome
Relapse-free survival (RFS)
Condition
Adenocarcinoma of Lung
Intervention
Furmonertinib
Study Arms / Comparison Groups
Furmonertinib
Description: ctDNA-MRD positive participants received 3 years of furmonertinib once daily as adjuvant therapy after radical surgery until disease progression or unacceptable toxicity occurs.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
50
Start Date
October 2021
Completion Date
September 2024
Primary Completion Date
March 2023
Eligibility Criteria
Inclusion Criteria:
1. Stage I lung adenocarcinoma patients underwent complete surgical resection with
negative margins (R0) and harbor sensitizing EGFR mutations (exon 19 and/or exon 21).
2. Positive ctDNA after surgery and prior to adjuvant therapy (4 weeks after surgery).
3. Completely recovered from surgery before adjuvant treatment and showed no signs of
tumor recurrence in imaging.
4. Adequate organ function: 1) Hemoglobin ≥ 9.0 g/dL; 2)Absolute neutrophil count (ANC) ≥
1500 cells/mm3; 3) Platelets ≥ 90,000/mm3; 4) AST, ALT ≤ 2.5 x ULN; 5) Total bilirubin
≤ 1.5 x ULN; 6) Serum creatinine ≤ 1.5x ULN and calculated creatinine clearance ≥
60ml/min.
5. Age >18 years old.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
7. Females must have a negative pregnancy test within 7 days prior to the start of dosing
if of child-bearing potential.
8. Males and females of reproductive potential who are sexually active must agree to use
adequate contraception prior to entry, during the process and 8 weeks after drug
withdrawal.
9. Written informed consent.
10. Compliance with the protocol.
11. Ability to swallow the formulated product.
Exclusion Criteria:
1. Any type of systemic anticancer therapy for lung adenocarcinomas, including
chemotherapy, targeted therapy or immunotherapy.
2. Any prior local radiotherapy for lung adenocarcinomas.
3. Clinical objective evidence (pathology or imaging) to confirm disease recurrence
before the start of adjuvant therapy.
4. Allergy to furmonertinib or any ingredients.
5. Past medical history of ILD, drug-induced ILD or any evidence of clinically active
ILD; CT scan at baseline revealed the presence of idiopathic pulmonary fibrosis.
6. Any evidence of uncontrolled systemic diseases, including active infection,
uncontrolled hypertension, unstable angina, angina within the last 3 months,
congestive heart failure (≥ New York Heart Association [NYHA] Grade II), myocardial
infarction (6 months before enrollment), severe arrhythmia requiring medical
treatment, liver diseases, kidney diseases or metabolic diseases.
7. Known history of human immunodeficiency virus (HIV) infection.
8. Pregnant or lactating women.
9. History of neurological or psychiatric disorders, including epilepsy or dementia.
10. Other judgments by the Investigator that the patient should not participate in the
study.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Fan Yang, MD, +86-010-88326657, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT05079022
Organization ID
Y-2021 AST/zd-0105
Responsible Party
Principal Investigator
Study Sponsor
Peking University People's Hospital
Collaborators
Beijing CSCO-Allist Cancer Research Foundation
Study Sponsor
Fan Yang, MD, Study Director, Peking University People's Hospital
Verification Date
October 2021