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

• ClinicalTrials.gov Identifier: NCT01621880
• Recruitment Status: Completed
• First Posted: June 18, 2012
• Results First Posted: November 26, 2018
• Last Update Posted: January 9, 2019
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Information provided by (Responsible Party): Yamei Tang, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Nasopharyngeal Carcinoma; Adverse Effect of Radiation Therapy; Brain Necrosis	Drug: bevacizumab; Drug: Corticosteroid	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Bevacizumab on Radiation-induced Brain Necrosis in Patients With Nasopharyngeal Carcinoma
• Actual Study Start Date: June 2012
• Actual Primary Completion Date: August 2015
• Actual Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Bevacizumab; 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.	Drug: bevacizumab; 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.; Other Name: Bevacizumab（Avastin）
Active Comparator: Corticosteroid; 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.	Drug: Corticosteroid; 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.; Other Name: methylprednisolone

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With a Treatment Response [ Time Frame: At 2 months. ]
   The primary outcome of the trial was the treatment response rate at two months. The definitions of response and progressive disease were based on both the radiographic changes and clinical symptoms. We defined response as both (1)a reduction in edema volume on FLAIR images by ≥25% and (2)no deteriorating symptoms. Progressive disease was defined as either (1)larger than 10% increase in the volume of the lesions; (2)appearance of any new lesion/site; or (3)clear clinical worsening.

Secondary Outcome Measures :

1. Percentage Change in Radiological Measures of Lesion Volume [ Time Frame: Change from baseline to evaluation at 2 months. ]
   T1 post-gadolinium imaging was used to measure the enhancement and T2-weighted FLAIR to measure the edema. For lesion measurements, radiologists used manual and semiautomatic approaches to identify the outline of the lesion, and the total volume was estimated with Volume Viewer 2 software(GE Healthcare, AW Suite2.0 6.5.1.z).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

China, Guangdong

Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, China, 510120

Sponsors and Collaborators

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Investigators

• Principal Investigator: Yamei Tang, Ph.D; Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Xu Y, Rong X, Hu W, Huang X, Li Y, Zheng D, Cai Z, Zuo Z, Tang Y. Bevacizumab Monotherapy Reduces Radiation-induced Brain Necrosis in Nasopharyngeal Carcinoma Patients: A Randomized Controlled Trial. Int J Radiat Oncol Biol Phys. 2018 Aug 1;101(5):1087-1095. doi: 10.1016/j.ijrobp.2018.04.068. Epub 2018 May 2.

• Responsible Party: Yamei Tang, Professor, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• ClinicalTrials.gov Identifier: NCT01621880
• Other Study ID Numbers: 2012025; SYSN001 ( Other Identifier: Sun Yat-sen Memorial Hospital, Neurology department )
• First Posted: June 18, 2012
• Results First Posted: November 26, 2018
• Last Update Posted: January 9, 2019
• Last Verified: December 2018

Keywords provided by Yamei Tang, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University:

radiation-induced brain necrosis; nasopharyngeal carcinoma; Bevacizumab; Methylprednisolone

Additional relevant MeSH terms:

Carcinoma; Nasopharyngeal Carcinoma; Necrosis; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Pathologic Processes; Methylprednisolone; Bevacizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents