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

Primary Purpose

Adenocarcinoma of Lung

Status

Not yet recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Furmonertinib

About this trial

This is an interventional treatment trial for Adenocarcinoma of Lung focused on measuring lung adenocarcinoma, circulating tumor DNA, minimal residual disease, EGFR, furmonertinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Stage I lung adenocarcinoma patients underwent complete surgical resection with negative margins (R0) and harbor sensitizing EGFR mutations (exon 19 and/or exon 21).
Positive ctDNA after surgery and prior to adjuvant therapy (4 weeks after surgery).
Completely recovered from surgery before adjuvant treatment and showed no signs of tumor recurrence in imaging.
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.
Age >18 years old.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
Females must have a negative pregnancy test within 7 days prior to the start of dosing if of child-bearing potential.
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.
Written informed consent.
Compliance with the protocol.
Ability to swallow the formulated product.

Exclusion Criteria:

Any type of systemic anticancer therapy for lung adenocarcinomas, including chemotherapy, targeted therapy or immunotherapy.
Any prior local radiotherapy for lung adenocarcinomas.
Clinical objective evidence (pathology or imaging) to confirm disease recurrence before the start of adjuvant therapy.
Allergy to furmonertinib or any ingredients.
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.
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.
Known history of human immunodeficiency virus (HIV) infection.
Pregnant or lactating women.
History of neurological or psychiatric disorders, including epilepsy or dementia.
Other judgments by the Investigator that the patient should not participate in the study.

Sites / Locations

Peking University People's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Furmonertinib

Arm 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT05079022

First Posted

September 9, 2021

Last Updated

October 3, 2021

Sponsor

Peking University People's Hospital

Collaborators

Beijing CSCO-Allist Cancer Research Foundation, Shanghai Allist Pharmaceutical Technology Co., Ltd., Guangzhou Burning Rock Medical Examination Institute Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT05079022

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Not yet recruiting

Study Start Date

October 2021 (Anticipated)

Primary Completion Date

March 2023 (Anticipated)

Study Completion Date

September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking University People's Hospital

Collaborators

Beijing CSCO-Allist Cancer Research Foundation, Shanghai Allist Pharmaceutical Technology Co., Ltd., Guangzhou Burning Rock Medical Examination Institute Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Adenocarcinoma of Lung

Keywords

lung adenocarcinoma, circulating tumor DNA, minimal residual disease, EGFR, furmonertinib

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Furmonertinib

Arm Type

Experimental

Arm 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.

Intervention Type

Drug

Intervention Name(s)

Furmonertinib

Other Intervention Name(s)

AST2818, AST5902

Intervention Description

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

Primary Outcome Measure Information:

Title

Clearance of ctDNA at 6 months

Description

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Relapse-free survival (RFS)

Description

Time Frame

Through study completion, an average of 3 years

Title

Clearance of ctDNA at 12 months

Description

Time Frame

12 months

Other Pre-specified Outcome Measures:

Title

Incidence of Treatment-Emergent Adverse Events

Description

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.

Time Frame

Through study completion, an average of 3 years

Title

Genomic changes of ctDNA

Description

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.

Time Frame

0, 3, 6, 12, 18, 24, 30, 36 months

Title

Relationship between radiomics features and ctDNA status

Description

To evaluate if the radiomics signatures on preoperative CT scans can be a prediction tool for the postoperative ctDNA-MRD status.

Time Frame

pre-surgery and 3 days after the surgery

Title

Relationship between radiomics features and clinical outcome

Description

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.

Time Frame

pre-surgery and through study completion (an average of 3 years)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Stage I lung adenocarcinoma patients underwent complete surgical resection with negative margins (R0) and harbor sensitizing EGFR mutations (exon 19 and/or exon 21). Positive ctDNA after surgery and prior to adjuvant therapy (4 weeks after surgery). Completely recovered from surgery before adjuvant treatment and showed no signs of tumor recurrence in imaging. 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. Age >18 years old. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Females must have a negative pregnancy test within 7 days prior to the start of dosing if of child-bearing potential. 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. Written informed consent. Compliance with the protocol. Ability to swallow the formulated product. Exclusion Criteria: Any type of systemic anticancer therapy for lung adenocarcinomas, including chemotherapy, targeted therapy or immunotherapy. Any prior local radiotherapy for lung adenocarcinomas. Clinical objective evidence (pathology or imaging) to confirm disease recurrence before the start of adjuvant therapy. Allergy to furmonertinib or any ingredients. 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. 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. Known history of human immunodeficiency virus (HIV) infection. Pregnant or lactating women. History of neurological or psychiatric disorders, including epilepsy or dementia. Other judgments by the Investigator that the patient should not participate in the study.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Fan Yang, MD

Phone

+86-010-88326657

yangfan@pkuph.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Fan Yang, MD

Organizational Affiliation

Peking University People's Hospital

Official's Role

Study Director

Facility Information:

Facility Name

Peking University People's Hospital

City

Beijing

ZIP/Postal Code

100044

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Fan Yang, MD

Phone

+86-010-88326657

yangfan@pkuph.edu.cn

First Name & Middle Initial & Last Name & Degree

Fan Yang, MD

First Name & Middle Initial & Last Name & Degree

Hao Li, MD

First Name & Middle Initial & Last Name & Degree

Heng Zhao, MD

First Name & Middle Initial & Last Name & Degree

Sida Cheng, MD

12. IPD Sharing Statement

Learn more about this trial

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

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