Effect of Edaravone on Radiation-induced Temporal Lobe Necrosis

Phase 2

Completed

• Conditions: Brain Necrosis; Nasopharyngeal Carcinoma
• Interventions: Drug: Edaravone; Other: Common fundamental management

• Registration Number: NCT01865201
• Lead Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Brief Summary

It is hypothesized that excessive generation of free radicals involves in the pathogenesis of radiation-induced brain necrosis. This study therefore evaluated the effect of free radical scavenger, edaravone, on radiation-induced temporal lobe necrosis (TLN) in patients with nasopharyngeal carcinoma (NPC) after radiotherapy.

Detailed Description

Radiation-induced temporal lobe necrosis (TLN) is the most serious sequelae of radiotherapy and impairs the patients' quality of life profoundly. Steroid is one of the conventional treatment methods for TLN. However, its response rate was still not so satisfactory (about 30%-35%).The mechanism of TLN is under exploring and not completely understood. It has been proposed recently that chronic oxidative stress and inflammation involve in the pathogenesis of radiation-induced late normal tissue injury.

Edaravone(3-methyl-1-phenyl-2-pyrazolin-5-one), which is proved to be an excellent free radical scavenger, has been applied to a wide range of oxidative stress-related diseases.Thus, it may exert a therapeutic effect on radiation-induced temporal lobe necrosis. To support this hypothesis, the investigators carried out a randomized study of combining edaravone with common fundamental management versus common fundamental therapy in patients with TLN, and analyzed the Late Effects of Normal Tissues -Subjective, Objective, Management, Analytic (LENT/SOMA) scale before and after treatment.

Study Timeline

• Study Start: 2009-03
• Primary Completion: 2011-10
• Study Completion: 2012-09
• Study First Submitted: 2013-05-26
• Study First Submitted QC: 2013-05-29
• Study First Posted: 2013-05-30
• Status Verified: 2013-12
• Last Update Submitted: 2013-12-11
• Last Update Posted: 2013-12-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 154

Inclusion Criteria

• ①Patients must have received radiation therapy for histologically confirmed nasopharyngeal carcinoma.

  • Prior irradiation >/= 6 months prior to study entry.

    • Radiographic evidence to support the diagnosis of radiation-induced temporal lobe necrosis without tumor recurrence(15).

      • Age>/= 18 years.

        • No evidence of very high intracranial pressure that suggests brain hernia and need surgery.

          • Fertile women who are willing to take contraception during the trial.

            • 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. prothrombin time(PT), activated partial thromboplastin time(APTT),international normalized ratio(INR) in a normal range.

              • Ability to understand and willingness to sign a written informed consent document.

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Exclusion Criteria

• ①Tumor recurrence or metastases.

  • Diseases of central nervous system, such as cerebral vascular events, inflammatory, degenerative disease, and significant cardiovascular diseases.

    • Severe systemic diseases.

      • History of anaphylactic response to edaravone.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Edaravone group	Edaravone	Edaravone was used at a dose of 30mg,intravenously, twice per day, for 14 days. All patients also received common fundamental management, which was as follows: ①Methylprednisolone, administered by intravenous infusion at a 500mg daily for 3 consecutive days and then gradually tailed off in 30 days with administration of oral prednisolone. ②Dehydration drugs.
Control group	Common fundamental management	All patients in this group received common fundamental management, which was as follows: ①Methylprednisolone, administered by intravenous infusion at a 500mg daily for 3 consecutive days and then gradually tailed off in 30 days with administration of oral prednisolone. ②Dehydration drugs.

Primary Outcome Measures

Name	Time	Method
The change of the maximum area of the necrosis lesion on MRI three months after treatment	At three months after treatment	The radiographic response was assessed by difference between MRI pretreatment and post-treatment, which included T1-weighted gadolinium contrast-enhanced and T2-weighted image. The maximum area measurement of the radiation necrosis lesions were recorded (the product of the longest trans diameter and its longest perpendicular). And the change of the maximum area of the necrosis lesion on MRI three months after treatment was used as the secondary end point.

Secondary Outcome Measures

Name	Time	Method
The change in LENT/SOMA scale scores at three months after treatment from base line	Three months after treatment	Clinical symptoms and signs were evaluated by Late Effects of Normal Tissues -Subjective, Objective, Management, Analytic (LENT/SOMA) scale(16) before drug administration and three months after treatment. Subjective domain contains five items: headache, somnolence, intellectual deficit, functional competence, and memory. Objective domain contains four items: neurologic deficit, cognitive functions, mood \& personality changes, and seizures. And Analytic domain includes neuropsychologic and radiologic assessments. Each domain scores from 0 to 4. The summary of each domain represents the final score of LENT/SOMA scale. The primary end point was the change in LENT/SOMA scale scores at three months after treatment from base line.

Trial Locations

Locations (1)

Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University; 🇨🇳 Guangzhou, Guangdong, China