ctDNA-MRD Based Adjuvant Targeted Therapy for EGFR Positive Stage I Lung Adenocarcinomas

NCT ID: NCT05079022

Last Updated: 2021-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-31

Study Completion Date

2024-09-30

Brief Summary

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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

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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.

Conditions

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Adenocarcinoma of Lung

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Furmonertinib

ctDNA-MRD positive participants received 3 years of furmonertinib once daily as adjuvant therapy after radical surgery until disease progression or unacceptable toxicity occurs.

Group Type EXPERIMENTAL

Furmonertinib

Intervention Type DRUG

Furmonertinib at 80mg dose will be administered orally once daily.

Interventions

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Furmonertinib

Furmonertinib at 80mg dose will be administered orally once daily.

Intervention Type DRUG

Other Intervention Names

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AST2818 AST5902

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Beijing CSCO-Allist Cancer Research Foundation

UNKNOWN

Sponsor Role collaborator

Shanghai Allist Pharmaceutical Technology Co., Ltd.

UNKNOWN

Sponsor Role collaborator

Guangzhou Burning Rock Medical Examination Institute Co., Ltd.

INDUSTRY

Sponsor Role collaborator

Peking University People's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Yangfan

Professor of Thoracic Surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Fan Yang, MD

Role: STUDY_DIRECTOR

Peking University People's Hospital

Locations

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Peking University People's Hospital

Beijing, , China

Site Status

Countries

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China

Central Contacts

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Fan Yang, MD

Role: CONTACT

+86-010-88326657

Facility Contacts

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Fan Yang, MD

Role: primary

+86-010-88326657

Other Identifiers

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Y-2021 AST/zd-0105

Identifier Type: -

Identifier Source: org_study_id