Clinical trial NCT04147728: Stereotactic Radiosurgery Combination With Anlotinib for Limited Brain Metastases With Perilesional Edema in NSCLC
Official title: Stereotactic Radiosurgery Combination With Anlotinib for Limited Brain Metastases With Perilesional Edema in Non-small Cell Lung Cancer：An Exploratory Single-Arm Phase II Clinical Trail
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Stereotactic Body Radiation Therapy
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
Collaborators: name: Huashan Hospital
name: Tianjin Medical University
First posted: 2019-11-01
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether stereotactic radiosurgery combination with Anlotinib is safe, effective in the treatment of limited brain metastases with Perilesional edema in non-small cell lung cancer.

Detailed description: The purpose of this study is to determine whether stereotactic radiosurgery combination with Anlotinib is safe, effective in the treatment of limited brain metastases with perilesional edema in non-small cell lung cancer. The sample size is 50. Patients start to take Anlotinib 1 week before the MRI-based simulation，12mg/d QD，day1\~14, day22\~36.Edema index will be used to evaluate the effectiveness of Anlotinib. The "Edema index (EI)" is calculated per the equation of "edema index= (peri-tumoral edema volume+ tumor volume)/tumor volume.

Eligibility criteria: Inclusion Criteria:

1. Patients voluntarily participate in this study, signed informed consent.
2. Patients pathologically diagnosed as non-small cell lung cancer, with brain metastases and measurable lesions;
3. Patients aged between 18 -80 years; with expected survival time\>3 months.
4. Patients with no more than 5 brain metastases
5. Patients with normal organ function within 7 days prior to treatment, the following criteria are met:

   a) blood routine examination criteria : i) hemoglobin (HB) ≥90g/L; ii) absolute neutrophil count (ANC) ≥1.5×10e9/L; iii) platelet (PLT) ≥80×10e9/L; b) biochemical tests meet the following criteria: i) total bilirubin (TBIL) ≤1.5 times of upper limit of normal (ULN); ii) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 ULN, if liver metastasis occurred, ALT and AST ≤5 ULN; iii) serum creatinine (Cr) ≤1.5 ULN or creatinine clearance (CCr) ≥60mL/min;
6. Female patients should agree to use contraceptives during and within 6 months after the study.

Exclusion Criteria:

1. Patients who had previously used antiangiogenic agents within 1 month;
2. Patients with small cell lung cancer (including small cell carcinoma and non-small cell carcinoma mixed lung cancer);
3. Patient with lung squamous cell carcinoma that involved pulmonary hilar, or non-small cell lung cancer with hemoptysis;
4. Patients with cerebral infarction and cerebral hemorrhage;
5. Patients without perilesional edema；
6. Patients with more than grade 2 (NCI-CTCAE v4.0) acute toxicity reaction due to any previous treatment.
7. Patients with factors that affect oral medication (such as cannot swallow, chronic diarrhea and intestinal obstruction, etc.);
8. Patients with visceral dissemination or severe symptoms, which could cause death in short term;
9. Patients with any other severe and/or uncontrolled disease;
10. Patients who received a surgery, a biopsy or a significant traumatic injury within 1 month;
11. Patients with any signs or medical history of bleeding, unhealed wounds, ulcers or fractures, regardless of the severity;
12. Patients underwent artery or venous thrombotic events within 2 months, such as deep vein thrombosis and pulmonary embolism;
13. Patients with a history of psychotropic medicine abuse and cannot quit or have mental disorders;
14. Patients with disease which will severely endanger their security and could not complete this study, according to the judgement of researchers；
15. Patients who still can't tolerate SRS after anlotinib treatment, even after adding mannitol, and have to receive steroid treatment.

Primary outcomes:
measure: EI
timeFrame: 1 month
Secondary outcomes:
measure: PFS
timeFrame: 1 year
measure: OS
timeFrame: 1 year
measure: ORR
timeFrame: 3 months
measure: DCR
timeFrame: 3 months
measure: iORR
timeFrame: 3 months
measure: iPFS
timeFrame: 3 months
measure: SRS rate
timeFrame: 1 month
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Radiation Oncology Cancer Center, Peking University Third Hospital 49# North Garden Rd.,Haidian Dist.
state: Beijing
Study officials:
affiliation: Peking University Third Hospital
name: Hongqing Zhuang, doctor
role: STUDY_DIRECTOR
References:
citation: Zhuang H, Wang Y, Cheng C, Shi S. The efficacy of anlotinib instead of glucocorticoids for edema induced by brain metastases in NSCLC patients with anti-PD1/PDL-1 immunotherapy. Neuro Oncol. 2021 Jan 30;23(1):169-171. doi: 10.1093/neuonc/noaa236. No abstract available.