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Effect and Safety of Apatinib on Radiation-Induced Brain Injury

Primary Purpose

Radiation Injuries

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Apatinib

About this trial

This is an interventional treatment trial for Radiation Injuries focused on measuring Apatinib, Radiation-induced brain injury

Eligibility Criteria

35 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female patients aged ≥35 years;
Prior radiotherapy for histologically confirmed head and neck cancer ≥12 months prior to study entry;
Radiographic evidence to support the diagnosis of radiation-induced brain injury without tumor recurrence;
Estimated life expectancy must be greater than 12 months;
Routine laboratory studies：Bilirubin ≤ 1.0 × upper limits of normal (ULN)； Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.0 × ULN；Creatinine <1.0 × ULN；White-cell count ≥ 4,000 cells per cubic millimeter；Neutrophils count ≥1500 cells per cubic millimeter；Platelets ≥100,000 cells per cubic millimeter；Hemoglobin ≥110 gram per milliliter；Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) within the normal ranges；
With sufficient cognitive function and language skills for communication and completion of study questionnaires;
Consent the enrollment of the study.

Exclusion Criteria:

Evidence of tumor metastasis, recurrence, or invasion;
Current usage of bevacizumab;
Current usage of glucocorticoids;
Evidence of very high intracranial pressure that suggests brain hernia and the need for surgery;
History of psychiatric disease before radiotherapy;
History of seizures;
History of arteriosclerotic cardiovascular diseases (ASCVD), e.g. stroke, myocardial infarction, and unstable angina, within 6 months;
Present or previous history of cardiac arrhythmia;
New York Heart Association Grade II or greater congestive heart failure;
Significant vascular disease, e.g. moderate or severe carotid stenosis, aortic aneurysm, and history of aortic dissection;
Severe infection;
History of allergy to relevant drugs;
Pregnancy, lactation, or fertility program in the following 12 months;
History or current diagnosis of peripheral nerve disease;
Abnormal liver and renal function;
Active tuberculosis;
A previous history of organ transplantation;
Infection with the human immunodeficiency virus;
Participation in other experimental studies;
Subjects with any other condition which in the investigator's judgment might intervene the outcome of the study.

Sites / Locations

Yamei TangRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Assigned Interventions

Arm Description

Apatinib with a dosage of 250mg once daily for 4 weeks, in the absence of unacceptable toxicity or severe deterioration.

Outcomes

Primary Outcome Measures

Overall efficacy rate

The proportion of patients with an objective response defined as ≥ 25% reduction in brain edema volume on Magnetic Resonance Imaging (MRI) fluid attenuated inversion recovery (FLAIR) images.

Secondary Outcome Measures

Change of brain necrosis

The proportion of patients with an objective response of brain necrosis defined as ≥ 25% reduction in the lesion volume of brain enhancement on post-gadolinium T1-weighted MR images.

Change in neurological function

The difference value of the Late Effects of Normal Tissue (LENT)-Subjective, Objective, Management, Analytic (SOMA) questionnaire before and after apatinib regimen. Score range: 0-4. The higher scores means worse outcome.

Change in the quality of life

The difference value of World Health Organization Quality of Lif (WHOQOL)-Bref scales before and after apatinib regimen. Score range:0-100. Higher scores represent better quality of life.

Change of white matter structural connectivity

Structural networks were weighted by measures of white matter microstructure of Neurite orientation dispersion and density imaging (NODDI) (fractional anisotropy, neurite density and orientation dispersion index) before and after apatinib regimen.

Change in cognitive function

The difference value of Montreal Cognitive Assessment (MoCA) scales before and after apatinib regimen. Score range:0-30. The higher scores represent better cognitive function.

Change in pain intensity

The difference value of Numerical rating scale (NRS) before and after apatinib regimen. Score range: 0-10. The higher scores indicate worse pain.

Full Information

NCT ID

NCT04152681

First Posted

October 22, 2019

Last Updated

November 3, 2019

Sponsor

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

1. Study Identification

Unique Protocol Identification Number

NCT04152681

Brief Title

Effect and Safety of Apatinib on Radiation-Induced Brain Injury

Official Title

Effect and Safety of Apatinib on Radiation-Induced Brain Injury: an Open-label, Single-arm, Phase 2 Study.

Study Type

Interventional

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Unknown status

Study Start Date

October 17, 2019 (Actual)

Primary Completion Date

February 2020 (Anticipated)

Study Completion Date

March 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Purpose: This early phase 2 clinical trial aims to evaluate the therapeutic effects and safety of apatinib in radiation-induced brain injury. Further study details as provided by Sun Yet-sen Memorial Hospital, Sun Yat-sen University / Yamei Tang. Primary outcome measure: The proportion of patients with an objective response defined as ≥ 25% reduction in brain edema volume on MR fluid attenuated inversion recovery (FLAIR) images.

Detailed Description

The incidence of nasopharyngeal carcinoma (NPC) is high in China especially in southern China. Radiotherapy is the mainstay of therapy for NPC and greatly improves patient survival. Along with promising therapeutic effects, complications such as radiation dermatitis, temporal lobe necrosis, cognitive impairment, and cranial nerve injury are also associated with radiotherapy. Previously, corticosteroids were considered conventional treatment for radiation-induced brain injury (RI). Unfortunately, only 20% patients with early phase RI seem to benefit from corticosteroid treatment. Moreover, the long-term use of steroids is associated with substantial adverse effects. Recently, bevacizumab, an anti-vascular endothelial growth factor (VEGF) recombinant monoclonal antibody, has been introduced as an efficient treatment for RI. However, the risk of severe adverse effects to bevacizumab, e.g. severe hypertension, proteinuria, nasopharyngeal necrosis and bleeding, limits its usage in certain patients with RI. Apatinib mesylate tablet is an oral small molecule tyrosine kinase inhibitor (TKI), which can specifically bind to vascular endothelial growth factor receptor 2 (VEGFR-2) and strongly inhibit neovascularization. Apatinib is currently used as a third-line treatment for advanced gastric cancer. Previous studies and clinical observation showed that apatinib could significantly improve brain injury after radiation, reduce brain tissue exudation and reduce edema. In this study, investigators will discuss the therapeutic effect of apatinib on RI and evaluate its safety through a prospective phase II clinical trial. It is hopeful to explore a new and effective method for the treatment of RI. Primary objectives: The primary objective of this phase II, open-label, single-arm designed clinical trial is to evaluate the efficacy and safety of apatinib in patients with RI. OUTLINE: This is a phase II, open-label, single-arm designed clinical trial. Participants are enrolled and administrated with oral apatinib mesylate tablet for 4 weeks. Arm 1: Participants receive oral apatinib with a dosage of 250mg once daily for 4 weeks, in the absence of unacceptable toxicity or severe deterioration.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Radiation Injuries

Keywords

Apatinib, Radiation-induced brain injury

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Assigned Interventions

Arm Type

Experimental

Arm Description

Apatinib with a dosage of 250mg once daily for 4 weeks, in the absence of unacceptable toxicity or severe deterioration.

Intervention Type

Drug

Intervention Name(s)

Apatinib

Intervention Description

Apatinib with a dosage of 250mg once daily for 4 weeks, in the absence of unacceptable toxicity or severe deterioration.

Primary Outcome Measure Information:

Title

Overall efficacy rate

Description

The proportion of patients with an objective response defined as ≥ 25% reduction in brain edema volume on Magnetic Resonance Imaging (MRI) fluid attenuated inversion recovery (FLAIR) images.

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

Change of brain necrosis

Description

The proportion of patients with an objective response of brain necrosis defined as ≥ 25% reduction in the lesion volume of brain enhancement on post-gadolinium T1-weighted MR images.

Time Frame

4 weeks

Title

Change in neurological function

Description

Time Frame

4 weeks

Title

Change in the quality of life

Description

The difference value of World Health Organization Quality of Lif (WHOQOL)-Bref scales before and after apatinib regimen. Score range:0-100. Higher scores represent better quality of life.

Time Frame

4 weeks

Title

Change of white matter structural connectivity

Description

Time Frame

4 weeks

Title

Change in cognitive function

Description

The difference value of Montreal Cognitive Assessment (MoCA) scales before and after apatinib regimen. Score range:0-30. The higher scores represent better cognitive function.

Time Frame

4 weeks

Title

Change in pain intensity

Description

The difference value of Numerical rating scale (NRS) before and after apatinib regimen. Score range: 0-10. The higher scores indicate worse pain.

Time Frame

4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

35 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female patients aged ≥35 years; Prior radiotherapy for histologically confirmed head and neck cancer ≥12 months prior to study entry; Radiographic evidence to support the diagnosis of radiation-induced brain injury without tumor recurrence; Estimated life expectancy must be greater than 12 months; Routine laboratory studies：Bilirubin ≤ 1.0 × upper limits of normal (ULN)； Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.0 × ULN；Creatinine <1.0 × ULN；White-cell count ≥ 4,000 cells per cubic millimeter；Neutrophils count ≥1500 cells per cubic millimeter；Platelets ≥100,000 cells per cubic millimeter；Hemoglobin ≥110 gram per milliliter；Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) within the normal ranges； With sufficient cognitive function and language skills for communication and completion of study questionnaires; Consent the enrollment of the study. Exclusion Criteria: Evidence of tumor metastasis, recurrence, or invasion; Current usage of bevacizumab; Current usage of glucocorticoids; Evidence of very high intracranial pressure that suggests brain hernia and the need for surgery; History of psychiatric disease before radiotherapy; History of seizures; History of arteriosclerotic cardiovascular diseases (ASCVD), e.g. stroke, myocardial infarction, and unstable angina, within 6 months; Present or previous history of cardiac arrhythmia; New York Heart Association Grade II or greater congestive heart failure; Significant vascular disease, e.g. moderate or severe carotid stenosis, aortic aneurysm, and history of aortic dissection; Severe infection; History of allergy to relevant drugs; Pregnancy, lactation, or fertility program in the following 12 months; History or current diagnosis of peripheral nerve disease; Abnormal liver and renal function; Active tuberculosis; A previous history of organ transplantation; Infection with the human immunodeficiency virus; Participation in other experimental studies; Subjects with any other condition which in the investigator's judgment might intervene the outcome of the study.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yamei Tang, M.D., Ph.D.

Phone

86-13556001992

yameitang@hotmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

lei He, M.D., Ph.D.

Phone

86-13560056821

fallmaple2008@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yamei Tang, M.D., Ph.D.

Organizational Affiliation

Sun Yat-sen Memorial Hospital,Sun Yat-sen University

Official's Role

Study Director

Facility Information:

Facility Name

Yamei Tang

City

Guanzhou

State/Province

Guangdong

ZIP/Postal Code

510120

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yamei Tang, M.D., Ph.D.

Phone

86-13556001992

yameitang@hotmail.com

First Name & Middle Initial & Last Name & Degree

lei He, M.D., Ph.D.

Phone

86-13560056821

fallmaple2008@163.com

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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Effect and Safety of Apatinib on Radiation-Induced Brain Injury

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