Stereotactic Radiosurgery Combination With Anlotinib for Limited Brain Metastases With Perilesional Edema in NSCLC (Rvision-001)

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

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.

Study Overview

• Status: Unknown
• Conditions: Stereotactic Body Radiation Therapy
• Intervention / Treatment: Drug: Anlotinib; Radiation: Stereotactic Radiosurgery

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 Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Recruiting
      • Department of Radiation Oncology Cancer Center, Peking University Third Hospital 49# North Garden Rd.,Haidian Dist.
      • Contact: Hongqing Zhuang, Doctor; Phone Number: 13051776232; Email: hongqingzhuang@163.com
      • Contact: Yuxia Wang, Doctor; Phone Number: 15001292991; Email: lily31415926@126.com
      • Principal Investigator: Enmin Wang
      • Principal Investigator: Yongchun Song
      • Sub-Investigator: Xin Wang
      • Sub-Investigator: Yun Guan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SRS Combination With Anlotinib; Stereotactic Radiosurgery Combination With Anlotinib	Drug: Anlotinib; Anlotinib is a novel multi-target tyrosine Kinase inhibitor that inhibits VEGFR2/3, FGFR1-4, PDGFD α/β, c-Kit and Ret.; Other Names: Antiangiogenic agents; Radiation: Stereotactic Radiosurgery; Stereotactic Radiosurgery as the initial treatment of non small cell lung cancer patients with limited brain metastases

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Peking University Third Hospital
• Collaborators: Huashan Hospital; Tianjin Medical University
• Investigators: Study Director: Hongqing Zhuang, doctor, Peking University Third Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2019
• Primary Completion (Anticipated): December 15, 2021
• Study Completion (Anticipated): December 15, 2022

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: October 31, 2019
• First Posted (Actual): November 1, 2019

Study Record Updates

• Last Update Posted (Actual): March 4, 2020
• Last Update Submitted That Met QC Criteria: March 1, 2020
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Angiogenesis Inhibitors
• Other Study ID Numbers: Rvision-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No