A Study of Furmonertinib Combined With Radiotherapy for Non-small Cell Lung Cancer With Oligoprogression

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase II Single-arm Study of Furmonertinib Combined With Radiotherapy for Non-small Cell Lung Cancer With Oligoprogression After First-line EGFR-TKI Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04970693
• Other study ID #: GASTO-1079
• Status: Recruiting
• Phase: Phase 2
• Start date: June 1, 2021
• Est. completion date: May 31, 2024

Study information

• Verified date: July 2021
• Source: Sun Yat-sen University
• Contact: Bo Qiu
• Phone: +86-020-87343031
• Email: qiubo[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase II randomized study is to explore the efficacy and safety of Furmonertinib combined with radiotherapy for non-small cell lung cancer with oligoprogression after first-line EGFR-TKI therapy.

Description:

This Phase II randomized study is to explore the efficacy and safety of Furmonertinib combined with radiotherapy for non-small cell lung cancer with oligoprogression after first-line EGFR-TKI therapy. The first group will enroll NSCLC patients with oligoprogression after using the first/second generation EGFR-TKI. The participants will receive Furmonertinib 80mg and local radiotherapy as the following therapy. The other group will enroll NSCLC patients with oligoprogression after using the third generation EGFR-TKI. The participants will receive Furmonertinib 160mg and local radiotherapy as the following therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: May 31, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients with locally advanced or metastatic NSCLC who are diagnosed by histology or cytology and are not suitable for surgery or radiotherapy;
• After receiving the first or second generation of EGFR-TKI treatment, the disease is oligoprogressive with 3-5 lesions (with imaging evidence), and the mutation is T790M+ (histological or hematological specimens, ARMS detection method);
• After receiving osimertinib treatment in the past, the disease is oligoprogressive with 3-5 lesions (with imaging evidence), and the patient refused chemotherapy;
• 18-80 years old;
• ECOG PS 0-2 scores;
• Organ and bone marrow functions were generally normal within 30 days before enrollment, including:AST, ALT = 2.5 × ULN or = 5 × ULN (with liver metastasis); total bilirubin = 1.5 × ULN; neutrophils absolute value = 1500 cells/mm3; Creatinine clearance =45 mL/min; Platelets = 100,000 cells/mm3; Hemoglobin =90g/L.
• The baseline has measurable lesions defined by the RECIST 1.1 standard, and the progressive lesions should be treated with local radiotherapy; the definition of the

lesion number includes:

1. When there are lesions on both adrenal glands, it is considered to be 2 metastases;

2. Two consecutive vertebral lesions and a paravertebral lesion within 6 cm can be considered as one metastasis, and the non-contiguous vertebral lesions should be counted separately;

3. The adjacent lesions in the liver, lung, and mediastinum can be considered as a metastasis if one isocenter can be used for irradiation;

4. Intracranial lesions are counted as 1 metastasis.

• The patient signed an informed consent form.

Exclusion Criteria:

• Severe or uncontrolled hypertension, diabetes, coronary artery stenosis, aortic dissection, aneurysm or acute bleeding disease;
• Any situation that increases the risk of QTc prolongation or arrhythmia;
• Left ventricular ejection fraction <50%;
• History of interstitial lung disease;
• FEV1%<30% or DLCO%<40%;
• Insertion of EGFR exon 20;
• The researcher believes that the patient is inappropriate to participate in this trial.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer
• Oligoprogressive

Intervention

Drug:
• Furmonertinib
The different dose of furmonertinib will be given according to the generation of EGFR-TKI used as the first-line therapy. The doses and target volume of radiotherapy will be decided according to the oligoprogressive sites.

Locations

Country	Name	City	State
China	Sun yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (9)

Eide IJZ, Helland Å, Ekman S, Mellemgaard A, Hansen KH, Cicenas S, Koivunen J, Grønberg BH, Brustugun OT. Osimertinib in T790M-positive and -negative patients with EGFR-mutated advanced non-small cell lung cancer (the TREM-study). Lung Cancer. 2020 May;143:27-35. doi: 10.1016/j.lungcan.2020.03.009. Epub 2020 Mar 12. — View Citation

Mu Y, Hao X, Xing P, Hu X, Wang Y, Li T, Zhang J, Xu Z, Li J. Acquired resistance to osimertinib in patients with non-small-cell lung cancer: mechanisms and clinical outcomes. J Cancer Res Clin Oncol. 2020 Sep;146(9):2427-2433. doi: 10.1007/s00432-020-03239-1. Epub 2020 May 8. — View Citation

Qiu B, Liang Y, Li Q, Liu G, Wang F, Chen Z, Liu M, Zhao M, Liu H. Local Therapy for Oligoprogressive Disease in Patients With Advanced Stage Non-small-cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutation. Clin Lung Cancer. 2017 Nov;18(6):e369-e373. doi: 10.1016/j.cllc.2017.04.002. Epub 2017 Apr 12. — View Citation

Schmid S, Klingbiel D, Aeppli S, Britschgi C, Gautschi O, Pless M, Rothschild S, Wannesson L, Janthur W, Foerbs D, Demmer I, Jochum W, Früh M. Patterns of progression on osimertinib in EGFR T790M positive NSCLC: A Swiss cohort study. Lung Cancer. 2019 Apr;130:149-155. doi: 10.1016/j.lungcan.2019.02.020. Epub 2019 Feb 19. — View Citation

Shah R, Lester JF. Tyrosine Kinase Inhibitors for the Treatment of EGFR Mutation-Positive Non-Small-Cell Lung Cancer: A Clash of the Generations. Clin Lung Cancer. 2020 May;21(3):e216-e228. doi: 10.1016/j.cllc.2019.12.003. Epub 2019 Dec 20. Review. — View Citation

Shi Y, Hu X, Zhang S, Lv D, Wu L, Yu Q, Zhang Y, Liu L, Wang X, Cheng Y, Ma Z, Niu H, Wang D, Feng J, Huang C, Liu C, Zhao H, Li J, Zhang X, Jiang Y, Gu C. Efficacy, safety, and genetic analysis of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small-cell lung cancer: a phase 2b, multicentre, single-arm, open-label study. Lancet Respir Med. 2021 Mar 26. pii: S2213-2600(20)30455-0. doi: 10.1016/S2213-2600(20)30455-0. [Epub ahead of print] — View Citation

Shi Y, Zhang S, Hu X, Feng J, Ma Z, Zhou J, Yang N, Wu L, Liao W, Zhong D, Han X, Wang Z, Zhang X, Qin S, Ying K, Feng J, Fang J, Liu L, Jiang Y. Safety, Clinical Activity, and Pharmacokinetics of Alflutinib (AST2818) in Patients With Advanced NSCLC With EGFR T790M Mutation. J Thorac Oncol. 2020 Jun;15(6):1015-1026. doi: 10.1016/j.jtho.2020.01.010. Epub 2020 Jan 30. Erratum in: J Thorac Oncol. 2020 Oct 16;:. — View Citation

Weickhardt AJ, Scheier B, Burke JM, Gan G, Lu X, Bunn PA Jr, Aisner DL, Gaspar LE, Kavanagh BD, Doebele RC, Camidge DR. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. J Thorac Oncol. 2012 Dec;7(12):1807-1814. doi: 10.1097/JTO.0b013e3182745948. — View Citation

Yu HA, Sima CS, Huang J, Solomon SB, Rimner A, Paik P, Pietanza MC, Azzoli CG, Rizvi NA, Krug LM, Miller VA, Kris MG, Riely GJ. Local therapy with continued EGFR tyrosine kinase inhibitor therapy as a treatment strategy in EGFR-mutant advanced lung cancers that have developed acquired resistance to EGFR tyrosine kinase inhibitors. J Thorac Oncol. 2013 Mar;8(3):346-51. doi: 10.1097/JTO.0b013e31827e1f83. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression-free survival	From the first day of treatment to the day of progression or the day of death.	2-year
Secondary	Overall survival	It was calculated from the first day of treatment to the day of death.	2-year
Secondary	Failure pattern	Disease progression such as local recurrence or distant metastasis.	2-year
Secondary	Safety evaluation	Adverse effects are graded according to the CTCAE 5.0 version, including multiple organs and tissues, such as gastrointestinal disease and symptom, cardiovascular disease, respiratory diseases and so on.	2 year after therapy