Clinical trial NCT05079022: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Adenocarcinoma of Lung
Keywords: lung adenocarcinoma
circulating tumor DNA
minimal residual disease
EGFR
furmonertinib
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
Collaborators: name: Beijing CSCO-Allist Cancer Research Foundation
name: Shanghai Allist Pharmaceutical Technology Co., Ltd.
name: Guangzhou Burning Rock Medical Examination Institute Co., Ltd.
First posted: 2021-10-15
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Clearance of ctDNA at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Relapse-free survival (RFS)
timeFrame: Through study completion, an average of 3 years
measure: Clearance of ctDNA at 12 months
timeFrame: 12 months
Other outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Through study completion, an average of 3 years
measure: Genomic changes of ctDNA
timeFrame: 0, 3, 6, 12, 18, 24, 30, 36 months
measure: Relationship between radiomics features and ctDNA status
timeFrame: pre-surgery and 3 days after the surgery
measure: Relationship between radiomics features and clinical outcome
timeFrame: pre-surgery and through study completion (an average of 3 years)
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
Study officials:
affiliation: Peking University People's Hospital
name: Fan Yang, MD
role: STUDY_DIRECTOR
References: