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

Phase 2

• Conditions: EGFR Positive Non-small Cell Lung Cancer; Brain Metastases
• Interventions: Drug: Almonertinib

• Registration Number: NCT04643847
• Lead Sponsor: First People's Hospital of Hangzhou

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2020-11
• Study First Submitted: 2020-11-15
• Study First Submitted QC: 2020-11-19
• Last Update Submitted: 2020-11-19
• Study First Posted: 2020-11-25
• Last Update Posted: 2020-11-25
• Study Start: 2020-11-30
• Primary Completion: 2022-11-30
• Study Completion: 2023-11-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 47

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Stereotactic radiosurgery with Almonertinib	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

Primary Outcome Measures

Name	Time	Method
Central nerve system duration of response（CNS DOR）	1 year	Central nerve system duration of response assessed by RANO-BM criteria

Secondary Outcome Measures

Name	Time	Method
overall survival (OS)	1 year	overall survival
Intracranial prgression-free survival(PFS)	1 year	Intracranial progression free survival assessed by Response Assessment in Neuro-Oncology Brain Metastases(RANO-BM) criteria
Intracranial response rate(RR）	1 year	Intracranial response rate assessed by RANO-BM criteria
Extracranial RR	1 year	Extracranial response rate assessed by Response Evaluation Criteria in Solid Tumors(RECIST) criteria
quality of life(QoL) assessed by EORTC QLQ-C30	1 year	Quality of Life assessed by The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30(EORTC QLQ-C30)
quality of life(QoL) assessed by EORTC QLQ-BN20	1 year	Quality of Life assessed by The European Organization for Reasearch and Treatment of Cancer Quality of Life Questionnaire Brain Cancer 20(BN20)
Neurocognitive function assessed by mini-mental state examination(MMSE) questionnaire score	1 year	Neurocognitive function assessed by mini-mental state examination(MMSE) questionnaire score

Trial Locations

Locations (1)

Hangzhou Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China