ctDNA-MRD Based Adjuvant Targeted Therapy for EGFR Positive Stage I Lung Adenocarcinomas
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|ClinicalTrials.gov Identifier: NCT05079022|
Recruitment Status : Not yet recruiting
First Posted : October 15, 2021
Last Update Posted : October 15, 2021
|Condition or disease||Intervention/treatment||Phase|
|Adenocarcinoma of Lung||Drug: Furmonertinib||Phase 1 Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Estimated Study Start Date :||October 2021|
|Estimated Primary Completion Date :||March 2023|
|Estimated Study Completion Date :||September 2024|
ctDNA-MRD positive participants received 3 years of furmonertinib once daily as adjuvant therapy after radical surgery until disease progression or unacceptable toxicity occurs.
Furmonertinib at 80mg dose will be administered orally once daily.
- Clearance of ctDNA at 6 months [ Time Frame: 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.
- Relapse-free survival (RFS) [ Time Frame: Through study completion, an average of 3 years ]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.
- Clearance of ctDNA at 12 months [ Time Frame: 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.
- Incidence of Treatment-Emergent Adverse Events [ Time Frame: Through study completion, an average of 3 years ]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.
- Genomic changes of ctDNA [ Time Frame: 0, 3, 6, 12, 18, 24, 30, 36 months ]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.
- Relationship between radiomics features and ctDNA status [ Time Frame: pre-surgery and 3 days after the surgery ]To evaluate if the radiomics signatures on preoperative CT scans can be a prediction tool for the postoperative ctDNA-MRD status.
- Relationship between radiomics features and clinical outcome [ Time Frame: pre-surgery and through study completion (an average of 3 years) ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05079022
|Contact: Fan Yang, MDemail@example.com|
|Peking University People's Hospital|
|Beijing, China, 100044|
|Contact: Fan Yang, MD +86-010-88326657 firstname.lastname@example.org|
|Principal Investigator: Fan Yang, MD|
|Sub-Investigator: Hao Li, MD|
|Sub-Investigator: Heng Zhao, MD|
|Sub-Investigator: Sida Cheng, MD|
|Study Director:||Fan Yang, MD||Peking University People's Hospital|