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

Sponsor

First People's Hospital of Hangzhou (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04643847

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
EGFR Positive Non-small Cell Lung Cancer Brain Metastases	Drug: Almonertinib	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

47 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Nov 30, 2020

Anticipated Primary Completion Date :

Nov 30, 2022

Anticipated Study Completion Date :

Nov 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
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	Drug: 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 (The number of lesions received SBRT and radiation dose are not standardized). Other Names: HS-10296

Arm

Intervention/Treatment

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

Drug: Almonertinib

Other Names:

HS-10296

Outcome Measures

Primary Outcome Measures

Central nerve system duration of response（CNS DOR） [1 year]
Central nerve system duration of response assessed by RANO-BM criteria

Secondary Outcome Measures

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
overall survival (OS) [1 year]
overall survival
Neurocognitive function assessed by mini-mental state examination(MMSE) questionnaire score [1 year]
Neurocognitive function assessed by mini-mental state examination(MMSE) questionnaire score
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)

Other Outcome Measures

Intracranial RR accessed by volumetric criteria [1 year]
Intracranial response rate accessed by volumetric criteria
intracranial progression rate assessed by brain MRI at 1year [1 year]
intracranial progression rate assessed by brain MRI at 1year

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or pathologically confirmed non-small-cell lung cancer (adenocarcinoma).
The presence of radiographically definite brain metastases and intracranial foci measurable according to the RANO-BM criteria.
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.
EGFR-sensitive mutations (include 19del or L858R mutation or coexist with other types of EGFR mutation).
Comply with the indications and drug instructions for first-line treatment with a third-generation EGFR-TKI.
Have not received systemic antineoplastic therapy, excluding neoadjuvant, adjuvant, or synchronous chemotherapy more than 6 months prior to enrollment.
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).
Age ≥ 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status(PS) score ≤ 2.
Survival is expected to be ≥ 6 months.
Women must use contraception after surgical sterilization, after sterilization, or during and for three months after treatment.
With informed consent signed.

Exclusion Criteria:

Previous treatment with almonertinib or other EGFR-TKI.
Patients with symptomatic brain metastases resulting in neurological deficits (not including headaches, nausea, or controlled seizures).
Multiple sclerosis.
Pacemakers implanted in the body or metals that cannot be examined by MRI.
Allergy to magnetic resonance contrast agents.
Brain metastases requiring surgical decompression.
Meningeal metastases.
Previous radiotherapy or surgery for brain metastases.
Contraindications to radiotherapy for uncontrolled systemic lupus erythematosus, scleroderma, or other connective tissue diseases.
Other malignant neoplasms (except non-melanoma skin cancer and cervical cancer) within five years.
Any medical or non-medical reason that prevents the patient from continuing to participate in research.
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.
Received studying drugs within 5 half-lives or 3 months, whichever is greater.
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).
The patient is taking any drug known to prolong the QT interval and cannot be discontinued until treatment with amitriptyline.
Pregnancy or breastfeeding.