Clinical trial NCT04643847: 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
Official title: Upfront Radiotherapy Combined With Almonertinib for Brain Metastasis in Non-small Cell Lung Cancer With EGFR Mutation: A Prospective Single-arm Phase II Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: EGFR Positive Non-small Cell Lung Cancer
Brain Metastases
Keywords: NSCLC
EGFR
Brain metastasis
Lead sponsor: First People's Hospital of Hangzhou
Sponsor class: OTHER
First posted: 2020-11-25
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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 cone beam computed tomography(CBCT) before each treatment). For patients who are assessed as oligometastasis three month after Almonertinib treatment, stereotactic body radiation therapy(SBRT) is recommended for oligometastatic lesions.
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Central nerve system duration of response（CNS DOR）
timeFrame: 1 year
Secondary outcomes:
measure: Intracranial prgression-free survival(PFS)
timeFrame: 1 year
measure: Intracranial response rate(RR）
timeFrame: 1 year
measure: Extracranial RR
timeFrame: 1 year
measure: overall survival (OS)
timeFrame: 1 year
measure: Neurocognitive function assessed by mini-mental state examination(MMSE) questionnaire score
timeFrame: 1 year
measure: quality of life(QoL) assessed by EORTC QLQ-C30
timeFrame: 1 year
measure: quality of life(QoL) assessed by EORTC QLQ-BN20
timeFrame: 1 year
Other outcomes:
measure: Intracranial RR accessed by volumetric criteria
timeFrame: 1 year
measure: intracranial progression rate assessed by brain MRI at 1year
timeFrame: 1 year
Locations:
city: Hangzhou
country: China
facility: Hangzhou Cancer Hospital
state: Zhejiang
Study officials:
References: