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

Adenocarcinoma of Lung Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05079022
• Other study ID #: Y-2021 AST/zd-0105
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: October 2021
• Est. completion date: September 2024

Study information

• Verified date: October 2021
• Source: Peking University People's Hospital
• Contact: Fan Yang, MD
• Phone: +86-010-88326657
• Email: yangfan[@]pkuph.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: September 2024
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Lung

Intervention

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

Locations

Country	Name	City	State
China	Peking University People's Hospital	Beijing

Sponsors (4)

Lead Sponsor	Collaborator
Peking University People's Hospital	Beijing CSCO-Allist Cancer Research Foundation, Guangzhou Burning Rock Medical Examination Institute Co., Ltd., Shanghai Allist Pharmaceutical Technology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of Treatment-Emergent Adverse Events	All patients who have received at least one dose furmonertinib will be regarded as the effective population for the safety analysis. Adverse events will be reported and graded in accordance with the NCI common adverse event terminology standard CTCAE version 5.0.	Through study completion, an average of 3 years
Other	Genomic changes of ctDNA	To dynamically evaluate the ctDNA profiles by next-generation sequencing and illustrate the genomic changes of ctDNA at baseline, during treatment, and at disease relapse.	0, 3, 6, 12, 18, 24, 30, 36 months
Other	Relationship between radiomics features and ctDNA status	To evaluate if the radiomics signatures on preoperative CT scans can be a prediction tool for the postoperative ctDNA-MRD status.	pre-surgery and 3 days after the surgery
Other	Relationship between radiomics features and clinical outcome	To evaluate if the radiomics signatures on preoperative CT scans can be a prediction tool for relapse-free survival of stage I lung adenocarcinoma patients with R0 resection.	pre-surgery and through study completion (an average of 3 years)
Primary	Clearance of ctDNA at 6 months	To estimate the percentage of patients with undetectable ctDNA at 6 months after adjuvant furmonertinib therapy in stage I lung adenocarcinoma patients who underwent R0 resection and have postoperatively detectable ctDNA prior to adjuvant therapy.	6 months
Secondary	Relapse-free survival (RFS)	To estimate RFS in all postoperative ctDNA-positive stage I lung adenocarcinoma patients, who underwent adjuvant furmonertinib therapy; To compare the RFS in postoperative ctDNA(+) patients who received adjuvant furmonertinib with that in postoperative ctDNA(-) patients, and with that in postoperative ctDNA(+) patients who didn't receive any adjuvant therapy, including chemotherapy, radiotherapy, targeted therapy or immunotherapy.	Through study completion, an average of 3 years
Secondary	Clearance of ctDNA at 12 months	To estimate the percentage of patients with undetectable ctDNA at 12 monthsafter adjuvant furmonertinib therapy in stage I lung adenocarcinoma patients who underwent R0 resection and have postoperatively detectable ctDNA prior to adjuvant therapy.	12 months