Effect of Bevacizumab on Radiation-induced Brain Necrosis in Patients With Nasopharyngeal Carcinoma (BRAIN)

Sun Yat-sen University

Status and phase: Completed; Phase 2

Conditions: Adverse Effect of Radiation Therapy; Nasopharyngeal Carcinoma; Brain Necrosis

Treatments: Drug: bevacizumab; Drug: Corticosteroid

Study type: Interventional

Funder types: Other

Identifiers

NCT01621880

2012025

SYSN001 (Other Identifier)

Details and patient eligibility

About

Bevacizumab may have a better effect on brain necrosis caused by radiotherapy.This randomized trial aims to investigate whether bevacizumab may alleviate radiation-induced brain necrosis in patients with nasopharyngeal carcinoma. The effect will be compared with outcomes in patients receiving steroid therapy.

Full description

Radiation-induced brain necrosis 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 bevacizumab can alleviate radiation-induced brain necrosis in patients with nasopharyngeal carcinoma, and to compare the treating effect between bevacizumab and steroid.

Enrollment: 112 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients must have received radiotherapy for histologically confirmed nasopharyngeal carcinoma.
• Prior irradiation >/= 6 months prior to study entry.
• Radiographic evidence to support the diagnosis of radiation-induced brain necrosis without tumor recurrence.
• Age>/= 18 years. Because on dosing or adverse event data are currently not available on the use of bevacizumab in patients <18years old.
• No prior bevacizumab therapy.
• No evidence of very high intracranial pressure that suggests brain hernia and needs surgery.
• Fertile women who are willing to take contraception during the trial.
• Routine laboratory studies with bilirubin </=upper limits of normal (ULN), aspartate aminotransferase (AST or SGOT) < ULN, creatinine <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.
• If with history of seizures, patients should be on anticonvulsant therapy. However, preference will be enzyme-non-inducing anticonvulsants.
• Ability to understand and willingness to sign a written informed consent document.
• 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

• Patients with any of the following should be excluded: 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.
• Evidence of active central nervous system hemorrhage.
• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to study enrollment.
• inadequately controlled hypertension (systolic blood pressure (SBP) > 140 mmHg and/or diastolic blood pressure (DBP) > 90 mmHg despite antihypertensive medication)
• 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.
• Evidence of bleeding diathesis or coagulopathy.
• Patients who have received steroid therapy for radiation-induced brain necrosis before the study.
• History of anaphylactic response to bevacizumab.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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112 participants in 2 patient groups

Bevacizumab

Active Comparator group

Description:

Patients receive bevacizumab 5mg/kg intravenously over 30-90 minutes on day1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: bevacizumab

Corticosteroid

Active Comparator group

Description:

Patients in the corticosteroid group were treated with intravenous pulsed-steroid therapy: methylprednisolone 500 mg daily intravenously for three consecutive days followed by oral prednisone 60 mg for five days and gradually tapered 15mg every 5 days. When the prednisone dose reached 30mg per day, it was tapered down more slowly (tapered 5mg every week), until a maintenance dose of 10mg per day was reached. The entire intervention lasted two months. At 2 months, prednisone was stopped.

Treatment:

Drug: Corticosteroid