Clinical trial NCT01621880: Effect of Bevacizumab on Radiation-induced Brain Necrosis in Patients With Nasopharyngeal Carcinoma
Official title: Effect of Bevacizumab on Radiation-induced Brain Necrosis in Patients With Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma
Adverse Effect of Radiation Therapy
Brain Necrosis
Keywords: radiation-induced brain necrosis
nasopharyngeal carcinoma
Bevacizumab
Methylprednisolone
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2012-06-18
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Number of Participants With a Treatment Response
timeFrame: At 2 months.
Secondary outcomes:
measure: Percentage Change in Radiological Measures of Lesion Volume
timeFrame: Change from baseline to evaluation at 2 months.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
state: Guangdong
Study officials:
affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
name: Yamei Tang, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.