Treatment of Bevacizumab Followed by Steroid in RN

Treatment of Bevacizumab Followed by Steroid in Radiation-induceded Brain Injury：a Randomized，Controlled and Single-blind Clinical Trail

Treatment of bevacizumab followed by steroid may have a better effect on patients with radiation-induced brain injury.This randomized trial aims to investigate whether treatment of bevacizumab followed by steroid may alleviate radiation-induced brain injury in patients with nasopharyngeal carcinoma. The effect will be compared with outcomes in patients receiving steroid therapy

Study Overview

• Status: Unknown
• Conditions: Brain Injuries; Nasopharyngeal Carcinoma; Adverse Effect of Radiation Therapy
• Intervention / Treatment: Drug: Bevacizumab and steroid; Drug: Bevacizumab and placebo

Detailed Description

Radiation-induced brain injury is a severe complication of radiotherapy in patients with Nasopharyngeal carcinoma. Current neuroprotective therapies show limited benefit in ameliorating this complication of radiotherapy. This study is a randomized, single blind clinical study. The primary aim of this study is to determine whether treatment of bevacizumab followed by steroid can alleviate radiation-induced brain injury in patients with nasopharyngeal carcinoma, and to compare the treating effect between combination of bevacizumab and steroid and bevacizumab alone.

• Study Type: Interventional
• Enrollment (Anticipated): 86
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Recruiting
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
      • Contact: Tang Yamei, Ph.D; Phone Number: 86-20-81332619

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must have received radiotherapy for histologically confirmed nasopharyngeal carcinoma.
2. Prior irradiation >/= 6 months prior to study entry.
3. Radiographic evidence to support the diagnosis of radiation-induced brain necrosis without tumor recurrence.
4. Age>/= 18 years. Because on dosing or adverse event data are currently not available on the use of bevacizumab in patients <18years old.
5. No prior bevacizumab therapy.
6. No evidence of very high intracranial pressure that suggests brain hernia and needs surgery.
7. Fertile women who are willing to take contraception during the trial.
8. Routine laboratory studies with bilirubin </=2 * upper limits of normal (ULN), aspartate aminotransferase (AST or SGOT) < 2 * ULN, creatinine <1.5 * ULN, red-cell count >/= 4,000 per cubic millimeter; white-cell count >/=1500 per cubic millimeter, platelets >/= 75,000 per cubic millimeter; Hb >/=9.0. PT, APTT, INR in a normal range.
9. If with history of seizures, patients should be on anticonvulsant therapy. However, preference will be enzyme-non-inducing anticonvulsants.
10. Ability to understand and willingness to sign a written informed consent document.
11. The patient has no active bleeding or pathological condition that carries a high risk of bleeding; there is no evidence of serious or non-healing wound, ulcer or bone fracture.

Exclusion Criteria:

1. evidence of metastatic disease;
2. evidence of tumor invasion to major vessels(e.g. the carotid);
3. history of bleeding related to tumor or radiotherapy during or after the completion of radiation.
4. Evidence of active central nervous system hemorrhage.
5. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to study enrollment.
6. inadequately controlled hypertension (systolic blood pressure (SBP) > 140 mmHg and/or diastolic blood pressure (DBP) > 90 mmHg despite antihypertensive medication)
7. Severe complications: 1) History of large vessel cerebrovascular accident (CVA) within 6 months; 2) Myocardial infarction or unstable angina within 6 months; 3) New York heart association grade II or greater congestive heart failure; 4) Serious and inadequately controlled cardiac arrhythmia; 5) Significant vascular disease (e.g. aortic aneurysm, history of aortic dissection); 6) Clinically significant peripheral vascular disease; 7) severe infection.
8. Evidence of bleeding diathesis or coagulopathy.
9. Patients who have received steroid therapy for radiation-induced brain necrosis before the study.
10. History of anaphylactic response to bevacizumab.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Bevacizumab and steroid; Bevacizumab 5mg / kg, once every two weeks, a total of 6 weeks of 4 courses, sequential prednisone 10mg / d orally, the total course of 12 weeks.	Drug: Bevacizumab and steroid; Bevacizumab 5mg / kg, once every two weeks, a total of 6 weeks of 4 courses, sequential prednisone 10mg / d orally, the total course of 12 weeks.
ACTIVE_COMPARATOR: Bevacizumab and placebo; Bevacizumab 5mg / kg, once every two weeks, a total of 6 weeks of 4 courses, sequential placebo 2 pills per day orally, the total course of 12 weeks.	Drug: Bevacizumab and placebo; Bevacizumab 5mg / kg, once every two weeks, a total of 6 weeks of 4 courses, sequential placebo 2 pills per day orally, the total course of 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in magnetic resonance imaging (MRI) of radiation-induced brain necrosis in patients	Change in MRI of radiation-induced brain necrosis in patients	Change form baseline to evaluation at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of neurologic function of patients after treatment	Change of neurologic function assessed using LENT/SOMA sacle of patients after treatment	Change from baseline to evaluation at 12 weks.
Change of quality of life of patients after treatment	Change of quality of life using QOL scale of patients after treatment	Change from baseline to evaluation at 12 weeks.

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Study Director: Tang Yamei, Ph.D, sun yat-sen memorial hospital,sun yat-sen universicy

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2016
• Primary Completion (ANTICIPATED): December 31, 2020
• Study Completion (ANTICIPATED): June 30, 2021

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: September 14, 2020
• First Posted (ACTUAL): September 17, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 17, 2020
• Last Update Submitted That Met QC Criteria: September 14, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Wounds and Injuries; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Craniocerebral Trauma; Trauma, Nervous System; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Brain Injuries; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: 20160101; SYS-2016004 (REGISTRY: Sun Yat-sen Memorial Hospital, Neurology department)

Plan for Individual participant data (IPD)

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