Stereotactic Radiosurgery Combination With Anlotinib for Limited Brain Metastases With Perilesional Edema in NSCLC

Phase 2

• Conditions: Stereotactic Body Radiation Therapy
• Interventions: Drug: Anlotinib; Radiation: Stereotactic Radiosurgery

• Registration Number: NCT04147728
• Lead Sponsor: Peking University Third Hospital

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.

Study Timeline

• Status Verified: 2019-10
• Study First Submitted: 2019-10-30
• Study First Submitted QC: 2019-10-31
• Study First Posted: 2019-11-01
• Study Start: 2019-12-24
• Last Update Submitted: 2020-03-01
• Last Update Posted: 2020-03-04
• Primary Completion: 2021-12-15
• Study Completion: 2022-12-15

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SRS Combination With Anlotinib	Anlotinib	Stereotactic Radiosurgery Combination With Anlotinib
SRS Combination With Anlotinib	Stereotactic Radiosurgery	Stereotactic Radiosurgery Combination With Anlotinib

Primary Outcome Measures

Name	Time	Method
EI	1 month	Edema Index. The "Edema index (EI)" is calculated per the equation of "edema index= (peri-tumoral edema volume+ tumor volume)/tumor volume.

Secondary Outcome Measures

Name	Time	Method
PFS	1 year	Progression-free Survival
OS	1 year	Overall Survival
ORR	3 months	Objective Response Rate
DCR	3 months	Disease Control Rate
iORR	3 months	intracranial objective response rate
iPFS	3 months	intracranial progression-free survival
SRS rate	1 month	the rate of SRS after anlotinib treatment

Trial Locations

Locations (1)

Department of Radiation Oncology Cancer Center, Peking University Third Hospital 49# North Garden Rd.,Haidian Dist.; 🇨🇳 Beijing, Beijing, China