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

NCT01621880 | Completed Phase 2 Results DMC

• 2 other identifiers: 2012025SYSN001
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

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.

Conditions

Nasopharyngeal Carcinoma; Adverse Effect of Radiation Therapy; Brain Necrosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Treatment Response

  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.

  At 2 months.

Secondary Outcomes (1)

• Percentage Change in Radiological Measures of Lesion Volume

  Change from baseline to evaluation at 2 months.

Study Arms (2)

Bevacizumab

ACTIVE COMPARATOR

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

Corticosteroid

ACTIVE COMPARATOR

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

Interventions

bevacizumab DRUG

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.

Also known as: Bevacizumab（Avastin）

Bevacizumab

Corticosteroid DRUG

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.

Also known as: methylprednisolone

Corticosteroid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

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

Guangzhou, Guangdong, 510120, China

Location

Related Publications (2)

• Luo S, Lai S, Wu Y, Hong J, Lin D, Lin S, Huang X, Xu X, Weng X. Cost-effectiveness analysis of bevacizumab for cerebral radiation necrosis treatment based on real-world utility value in China. Strahlenther Onkol. 2024 Sep;200(9):805-814. doi: 10.1007/s00066-024-02242-6. Epub 2024 Jun 3.

  PMID: 38829437 DERIVED

• 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.

  PMID: 29885994 DERIVED

MeSH Terms

Conditions

Nasopharyngeal Carcinoma; Radiation Injuries

Interventions

Bevacizumab; Adrenal Cortex Hormones; Methylprednisolone

Condition Hierarchy (Ancestors)

Carcinoma; 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; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Yamei Tang
• Organization: Sun Yat-sen Memorial Hospital, Sun Yat-sen University

yameitang@hotmail.com

08613556001992

Study Officials

• Yamei Tang, Ph.D

  Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 14, 2012
• First Posted: June 18, 2012
• Study Start: June 1, 2012
• Primary Completion: August 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 9, 2019
• Results First Posted: November 26, 2018

Record last verified: 2018-12

Locations

CN (1)