Effect of Edaravone on Radiation-induced Temporal Lobe Necrosis

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Effect of Edaravone on Radiation-induced Temporal Lobe Necrosis in Patients With Nasopharyngeal Carcinoma After Radiotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01865201
• Other study ID #: 2009001
• Status: Completed
• Phase: Phase 2
• First received: May 26, 2013
• Last updated: December 11, 2013
• Start date: March 2009
• Est. completion date: September 2012

Study information

• Verified date: December 2013
• Source: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: September 2012
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• ?Patients 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.

Exclusion Criteria:

• ?Tumor 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Necrosis
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms
• Necrosis

Intervention

Drug:
• Edaravone
Be used at a dose of 30mg, intravenously, twice per day, for 14 days.

Other:
• Common fundamental management
common fundamental management, which was as follows: ?Methylprednisolone, 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. ?Dehydration drugs.

Locations

Country	Name	City	State
China	Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The change of the maximum area of the necrosis lesion on MRI 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.	At three months after treatment	No
Secondary	The change in LENT/SOMA scale scores at three months after treatment from base line	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.	Three months after treatment	No

External Links

•   The homepage of Sun Yat-sen Memorial Hospital, Sun Yat-sen University