A Phase II Trial of Upfront Radiotherapy Plus Almonertinib for Epidermal Growth Factor Receptor(EGFR)-Mutant Non-small-cell Lung Cancer(NSCLC) Patients With Brain Metastases

Study Purpose

Almonertinib is a three-generation epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI), which has shown competitive potential in the second-line treatment against first-generation TKIs. This study intends to assess the efficacy and safety of stereotactic radiosurgery with sequential almonertinib in treatment-naive EGFR-mutant NSCLC patients with brain metastases.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Histologically or pathologically confirmed non-small-cell lung cancer (adenocarcinoma). 2. The presence of radiographically definite brain metastases and intracranial foci measurable according to the RANO-BM criteria. 3. The number of brain metastases ≤ 10, the volume of individual metastases ≤ 15 cc, the diameter of individual metastases ≤ 30 mm, the diameter of metastases in the brainstem ≤ 5 mm, distance of the foci from the optic nerve, or optic cross > 5 mm. 4. EGFR-sensitive mutations (include 19del or L858R mutation or coexist with other types of EGFR mutation). 5. Comply with the indications and drug instructions for first-line treatment with a third-generation EGFR-TKI. 6. Have not received systemic antineoplastic therapy, excluding neoadjuvant, adjuvant, or synchronous chemotherapy more than 6 months prior to enrollment. 7. Asymptomatic or mildly symptomatic brain metastases (e.g., headache, nausea, or seizures for which dexamethasone/analgesic/antiepileptic medication is effective and sustained at a steady dose for 3 days or more). 8. Age ≥ 18 years. 9. Eastern Cooperative Oncology Group (ECOG) performance status(PS) score ≤ 2. 10. Survival is expected to be ≥ 6 months. 11. Women must use contraception after surgical sterilization, after sterilization, or during and for three months after treatment. 12. With informed consent signed.

Exclusion Criteria:

1. Previous treatment with almonertinib or other EGFR-TKI. 2. Patients with symptomatic brain metastases resulting in neurological deficits (not including headaches, nausea, or controlled seizures). 3. Multiple sclerosis. 4. Pacemakers implanted in the body or metals that cannot be examined by MRI. 5. Allergy to magnetic resonance contrast agents. 6. Brain metastases requiring surgical decompression. 7. Meningeal metastases. 8. Previous radiotherapy or surgery for brain metastases. 9. Contraindications to radiotherapy for uncontrolled systemic lupus erythematosus, scleroderma, or other connective tissue diseases. 10. Other malignant neoplasms (except non-melanoma skin cancer and cervical cancer) within five years. 11. Any medical or non-medical reason that prevents the patient from continuing to participate in research. 12. It is expected that the patient will not be able to comply with the procedures, restrictions, and requirements of the study and the investigator determines that the patient is unfit to participate in the study. 13. Received studying drugs within 5 half-lives or 3 months, whichever is greater. 14. Currently receiving drugs or herbal supplements known to be potent inducers of Cytochrome P450 3A4(CYP3A4) or unable to be discontinued prior to receiving the first dose of study treatment) (at least 3 weeks prior). 15. The patient is taking any drug known to prolong the QT interval and cannot be discontinued until treatment with amitriptyline. 16. Pregnancy or breastfeeding.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04643847
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	First People's Hospital of Hangzhou
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries	China
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	EGFR Positive Non-small Cell Lung Cancer, Brain Metastases

Arms & Interventions

Arms

Experimental: Stereotactic radiosurgery with Almonertinib

110mg Almonertinib is administered orally daily since the first day after stereotactic radiosurgery treatment (total dose 30 Gy, 5 fractions, day1, 3, 5, calibrated by CBCT before each treatment). For patients who are assessed as oligometastasis three months after Almonertinib treatment, SBRT is recommended for oligometastatic lesions

Interventions

Drug: - Almonertinib

Contact a Trial Team

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