Non-Small Cell Lung Cancer (NSCLC)
Conditions
Keywords
Almonertinib, Radiotherapy, Brain Metastasis, Non-Small Cell Lung Cancer, Intracranial Progress Free Survival
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).
Detailed description
All eligible patients will receive craniocerebral radiotherapy in combination with Almonertinib. Here are two types of craniocerebral radiotherapy: 1. SRS or SRT is recommended for patients with ≤4 intracranial metastases and the maximum lesion ≤4cm. 24-15 Gy\*1F was recommended if use SRS. 9-12 Gy\*3F or 6Gy×5F was recommended if use SRT. 2. For \>4 intracranial metastases, or the maximum lesion\>4cm, whole-brain radiotherapy (WBRT) of 30Gy/10F was recommended, and then the large residual lesions will be treated with a local dose (≤DT 45Gy/15F). Hippocampal protection is highly recommended.
Interventions
DRUGAlmonertinib
Almonertinib 110mg p.o qd. Treatment with Almonertinib will continue until progression or unacceptable toxicity.
RADIATIONStereotactic Radiotherapy(SRT) or Stereotactic Radiosurgery(SRS) or Whole-Brain Radiotherapy(WBRT)
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).
Sponsors
Chongqing University Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-75 years old (calculated from the time when the subject signed the informed consent), both male and female. 2. Confirmed pathology of EGFR mutation positive（exon 19 deletion, L858R, T790M）NSCLC with brain metastases on enhanced MRI. 3. Subjects had not previously received chemotherapy, EGFR-TKI, biologic or immunotherapy, or other experimental therapy as first-line treatment for advanced NSCLC. 4. 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. 5. ECOG PS score: 0-1 points. 6. Must be able to swallow tablets，and expected survival ≥3 months. 7. Clinical diagnosis of Alzheimer's patients who can be treated with radiation therapy. 8. 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: 1. 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; 2. 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); * ALP≤2.5×ULN (such as tumor bone metastases, ≤5×ULN); * TBiL≤1.5×ULN. * ALB≥30 g/L; * Cr≤1.5×ULN, while creatinine clearance (CrCL)≥60 mL/min (Cockcroft - Gault formula); * APTT≤1.5×ULN, at the same time of INR or PT≤1.5×ULN (without anticoagulation therapy). 9. Women of childbearing age must have a serum pregnancy test within 3 days prior to the first dose and the results are negative.Women of reproductive age subjects and male subjects whose partners are women of reproductive age must agree to use barrier contraception (i.e., condoms) during the study period and for 180 days after the last administration of the study drug. 10. Volunteered to participate in clinical studies and signed informed consent.
Exclusion criteria
1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intracranial Progress Free Survival(iPFS) | Up to 4 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of adverse events of grade 3-4 or higher | Up to 4 years | To estimate and compare rates of ≥ grade 3-4 adverse events, by organ system, by CTCAEv4.0 that occur within 3 months from the start of craniocerebral radiotherapy when given prior to or concurrently with Almonertinib. |
| Rate of long term adverse events | Up to 4 years | To estimate and compare the rates of long-term adverse events (after 3 months) from the end of craniocerebral radiotherapy when given prior to or concurrently with Almonertinib. |
| Rate of change in tumor microenvironment | Up to 4 years | To evaluate and compare changes in the tumor microenvironment induced by radiation when given prior to or concurrently with Almonertinib. |
| Changes in EGFR mutations | Up to 4 years | To evaluate whether response to therapy correlates with changes in EGFR mutations among patients treated with Almonertinib combined with craniocerebral radiotherapy. |
| Overall Survival | Up to 4 years | Time from entry to death from any cause (the last follow-up time for patients lost to follow-up; Patients who were still alive at the end of the study, the end date of follow-up). |
Countries
China
Contacts
Primary ContactDingyi Yang, M.D.
Backup ContactYing Wang, Ph.D, M.D.
Outcome results
None listed