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

NCT04643847 | Unknown Phase 2

• 1 other identifier: AlmonRad
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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.

Conditions

EGFR Positive Non-small Cell Lung Cancer; Brain Metastases

Keywords

NSCLC; EGFR; Brain metastasis

Outcome Measures

Primary Outcomes (1)

• Central nerve system duration of response（CNS DOR）

  Central nerve system duration of response assessed by RANO-BM criteria

  1 year

Secondary Outcomes (7)

• Intracranial prgression-free survival(PFS)

  1 year

• Intracranial response rate(RR）

  1 year

• Extracranial RR

  1 year

• overall survival (OS)

  1 year

• Neurocognitive function assessed by mini-mental state examination(MMSE) questionnaire score

  1 year

Other Outcomes (2)

• Intracranial RR accessed by volumetric criteria

  1 year

• intracranial progression rate assessed by brain MRI at 1year

  1 year

Study Arms (1)

Stereotactic radiosurgery with Almonertinib

EXPERIMENTAL

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

Interventions

Almonertinib DRUG

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).

Also known as: HS-10296

Stereotactic radiosurgery with Almonertinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• First People's Hospital of Hangzhou: lead

Study Sites (1)

Hangzhou Cancer Hospital

Hangzhou, Zhejiang, 310002, China

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

aumolertinib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Bing Xia, MD

CONTACT

86 571 56006388; bxia_hzch@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 15, 2020
• First Posted: November 25, 2020
• Study Start: November 30, 2020
• Primary Completion: November 30, 2022
• Study Completion: November 30, 2023
• Last Updated: November 25, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)