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

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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