Almonertinib Combined With Cerebral Radiation Treat Brain Metastases From EGFR Positive NSCLC

NCT04905550 | Unknown Phase 2 DMC

• 1 other identifier: RadiAl-CNS
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

According to literature reports, about 16.3%-19% of newly diagnosed NSCLC patients are associated with brain metastasis, and 30%-50% of NSCLC patients will develop brain metastasis during the whole course of the disease. Patients with EGFR positive-type had a 10-15% higher risk of brain metastasis than patients with EGFR wild-type. mOS in patients with EGFR positive were twice as high as those with EGFR wild-type, despite the presence of brain metastasis. Improving the control rate of intracranial lesions in patients with EGFR positive can not only improve the quality of life, but also may translate into survival benefits and improve OS. Previous studies have shown that in lung cancer patients with EGFR-sensitive mutations, craniocerebral radiotherapy prior to delayed craniocerebral radiotherapy significantly prolonged OS. The first-line treatment of the third generation of EGFR-TKI targeting drug Almonertinib for EGFR-positive NSCLC can eliminate the possible EGFR T790M mutant clones at an early stage and better control the disease progression. Moreover, Almonertinib is easy to pass through the blood-brain barrier, which can not only better control intracranial lesions, but also control, prevent or delay the occurrence of brain metastasis. This study was intended to conduct a randomized controlled study on the safety and efficacy of early craniocerebral radiotherapy combined with Almonertinib in patients with EGFR positive non-small cell lung cancer with brain metastasis. Through the above studies we hope to confirm that early craniocerebral radiotherapy combined with Almonertinib is safe and feasible for patients with EGFR positive newly diagnosed with brain metastasis, and can prolong the intracranial progression-free survival (IPFS), and even extend the progression-free survival (PFS) and overall survival (OS).

Conditions

Non-Small Cell Lung Cancer (NSCLC)

Keywords

Almonertinib; Radiotherapy; Brain Metastasis; Non-Small Cell Lung Cancer; Intracranial Progress Free Survival

Outcome Measures

Primary Outcomes (1)

• Intracranial Progress Free Survival(iPFS)

  As determined by the investigator using RECIST 1.1 criteria between patients receiving Almonertinib and craniocerebral radiotherapy. iPFS is defined as The time between the start of treatment and the observation of progression of intracranial lesions or death from any cause. In order to ascertain this endpoint, efforts will be made so that patients will be followed for 156 weeks or until progression of disease (and treatment cessation), whichever comes first. At each time-point, subjects should have CT/MR of chest and head with contrast.

  Up to 4 years

Secondary Outcomes (5)

• Number of adverse events of grade 3-4 or higher

  Up to 4 years

• Rate of long term adverse events

  Up to 4 years

• Rate of change in tumor microenvironment

  Up to 4 years

• Changes in EGFR mutations

  Up to 4 years

• Overall Survival

  Up to 4 years

Study Arms (1)

Craniocerebral radiotherapy combined with Almonertinib 110mg p.o qd

EXPERIMENTAL

Almonertinib mesylate tablet, 110mg, qd; until the disease progresses or unacceptable toxicity. The craniocerebral radiotherapy was acceptable from 1 week before to 6 weeks after treatment with Almonertinib. Dose adjustment and delay of Almonertinib are allowed. Delay of Almonertinib is allowed for up to 9 weeks, calculated from the time of last administration, otherwise, treatment is terminated.

Drug: Almonertinib; Radiation: Stereotactic Radiotherapy(SRT) or Stereotactic Radiosurgery(SRS) or Whole-Brain Radiotherapy(WBRT)

Interventions

Almonertinib DRUG

Almonertinib 110mg p.o qd. Treatment with Almonertinib will continue until progression or unacceptable toxicity.

Also known as: The third generation of EGFR - TKI

Craniocerebral radiotherapy combined with Almonertinib 110mg p.o qd

Stereotactic Radiotherapy(SRT) or Stereotactic Radiosurgery(SRS) or Whole-Brain Radiotherapy(WBRT) RADIATION

Image guided, 24-15 Gy\*1F was recommended if use SRS. 9-12 Gy\*3F/1W or 6Gy×5F/1W was recommended if use SRT. 30Gy/10F/2W for WBRT, large residual lesions will be treated with a local dose (≤DT 45Gy/15F).

Craniocerebral radiotherapy combined with Almonertinib 110mg p.o qd

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years old (calculated from the time when the subject signed the informed consent), both male and female.
• Confirmed pathology of EGFR mutation positive（exon 19 deletion, L858R, T790M）NSCLC with brain metastases on enhanced MRI.
• Subjects had not previously received chemotherapy, EGFR-TKI, biologic or immunotherapy, or other experimental therapy as first-line treatment for advanced NSCLC.
• According to RECIST 1.1 criteria, subjects must have a measurable target lesion (maximum diameter under MRI/CT ≥10mm, short diameter of lymph node ≥15mm) that has been examined by CT or MRI.Tumor imaging evaluation was performed within 28 days prior to initial treatment.
• ECOG PS score: 0-1 points.
• Must be able to swallow tablets，and expected survival ≥3 months.
• Clinical diagnosis of Alzheimer's patients who can be treated with radiation therapy.
• All screening laboratory tests are performed according to protocol and need to be performed within 14 days prior to the first dose.The values of laboratory tests performed by screening must meet the following criteria:
• Routine blood examination :(no blood transfusion, no G-CSF, no drug correction within 14 days before screening)
• Hemoglobin (Hb) ≥90 g/L;
• Absolute neutrophil count (ANC) ≥1.5×109/L;
• Platelet count (PLT) ≥100×109/L;
• White blood cell count (WBC) ≥4.0×109/L and ≤15×109/L;
• Biochemical test :(no blood transfusion or albumin within 14 days prior to screening)
• AST and ALT ≤1.5×ULN (such as cancer that has spread to the liver, ≤5×ULN);

You may not qualify if:

• Subjects who had previously received anti-EGFR-TKI therapy.
• Patients with neuromeningeal disease but no intracranial metastases confirmed by MRI and/or CSF malignancy.
• Previous radiotherapy for CNS metastases, including measurable or unmeasurable sites of the disease for efficacy assessment.
• Patients who had undergone a major surgical procedure (other than placement of vascular access or CNS shunt) or had a major traumatic injury or were expected to require major surgery during the study period within 4 weeks prior to initial dosing.
• Subject who can be surgically excised or treated with radical radiotherapy.
• History and complications:
• The patient is using (or cannot be discontinued for at least 1 week prior to the first dosing of the investigational treatment) some drug or herbal supplement known to be a strong depressant or inducer of CYP3A4/5 (Appendix 8).
• Excluding uncontrollable nausea and vomiting, chronic gastrointestinal disease, prior gastrectomy or other surgery, may affect the full absorption of the study drug.
• exclude the presence of any serious or uncontrolled systemic disease or condition, including:
• Uncontrolled high blood pressure, diabetes, thyroid disease;
• Severe heart, lung or kidney disease;
• Active bleeding constitution;
• Any bacterial, viral, fungal or other active infection that the Investigator considers to pose a serious risk to the patient;
• Active hepatitis (HBsAg positive or HBcAb positive, HBV DNA positive), or HCV antibody positive or HIV positive.
• Patients with unstable symptomatic metastases: Any unstable and symptomatic CNS or distant metastases that were not controlled by previous surgery, radiotherapy, or corticosteroid treatment within 2 weeks prior to the initial study treatment.Corticosteroids were used before treatment for CNS symptoms, but the symptoms were controllable after treatment, and corticosteroids were used during radiotherapy.

Sponsors & Collaborators

• Chongqing University Cancer Hospital: lead

Study Sites (1)

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, 400030, China

RECRUITING

Related Publications (11)

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  PMID: 32357848 BACKGROUND

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  PMID: 32916310 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

aumolertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Ying Wang, Ph.D, M.D.

  Chongqing University Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dingyi Yang, M.D.

CONTACT

15123117697; dingyiyang@cqu.edu.cn

Ying Wang, Ph.D, M.D.

CONTACT

13996412826; yingwang197011@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director of Chongqing University Cancer Hospital

Study Record Dates

• First Submitted: May 23, 2021
• First Posted: May 27, 2021
• Study Start: March 1, 2021
• Primary Completion: March 1, 2024
• Study Completion: August 1, 2024
• Last Updated: June 2, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)