Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05079022
Recruitment Status : Not yet recruiting
First Posted : October 15, 2021
Last Update Posted : October 15, 2021
Sponsor:
Collaborators:
Beijing CSCO-Allist Cancer Research Foundation
Shanghai Allist Pharmaceutical Technology Co., Ltd.
Guangzhou Burning Rock Medical Examination Institute Co., Ltd.
Information provided by (Responsible Party):
Yangfan, Peking University People's Hospital

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.

Condition or disease Intervention/treatment Phase
Adenocarcinoma of Lung Drug: Furmonertinib Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Furmonertinib
Furmonertinib at 80mg dose will be administered orally once daily.
Other Names:
  • AST2818
  • AST5902




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.


Other Outcome Measures:
  1. 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.

  2. 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.

  3. 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.

  4. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Fan Yang, MD +86-010-88326657 yangfan@pkuph.edu.cn

Locations
Layout table for location information
China
Peking University People's Hospital
Beijing, China, 100044
Contact: Fan Yang, MD    +86-010-88326657    yangfan@pkuph.edu.cn   
Principal Investigator: Fan Yang, MD         
Sub-Investigator: Hao Li, MD         
Sub-Investigator: Heng Zhao, MD         
Sub-Investigator: Sida Cheng, MD         
Sponsors and Collaborators
Peking University People's Hospital
Beijing CSCO-Allist Cancer Research Foundation
Shanghai Allist Pharmaceutical Technology Co., Ltd.
Guangzhou Burning Rock Medical Examination Institute Co., Ltd.
Investigators
Layout table for investigator information
Study Director: Fan Yang, MD Peking University People's Hospital
Layout table for additonal information
Responsible Party: Yangfan, Professor of Thoracic Surgery, Peking University People's Hospital
ClinicalTrials.gov Identifier: NCT05079022    
Other Study ID Numbers: Y-2021 AST/zd-0105
First Posted: October 15, 2021    Key Record Dates
Last Update Posted: October 15, 2021
Last Verified: October 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Yangfan, Peking University People's Hospital:
lung adenocarcinoma
circulating tumor DNA
minimal residual disease
EGFR
furmonertinib
Additional relevant MeSH terms:
Layout table for MeSH terms
Adenocarcinoma
Adenocarcinoma of Lung
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Aflutinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action