Effect and Safety of Apatinib on Radiation-Induced Brain Injury

November 3, 2019 updated by: Yamei Tang, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

36

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guanzhou, Guangdong, China, 510120

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Assigned Interventions
Apatinib with a dosage of 250mg once daily for 4 weeks, in the absence of unacceptable toxicity or severe deterioration.
Drug: Apatinib
Apatinib with a dosage of 250mg once daily for 4 weeks, in the absence of unacceptable toxicity or severe deterioration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall efficacy rate
Time Frame: 4 weeks
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.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of brain necrosis
Time Frame: 4 weeks
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.
4 weeks
Change in neurological function
Time Frame: 4 weeks
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.
4 weeks
Change in the quality of life
Time Frame: 4 weeks

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.
4 weeks
Change of white matter structural connectivity
Time Frame: 4 weeks
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.
4 weeks
Change in cognitive function
Time Frame: 4 weeks
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.
4 weeks
Change in pain intensity
Time Frame: 4 weeks
The difference value of Numerical rating scale (NRS) before and after apatinib regimen. Score range: 0-10. The higher scores indicate worse pain.
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Investigators

  • Study Director: Yamei Tang, M.D., Ph.D., Sun Yat-sen Memorial Hospital,Sun Yat-sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 17, 2019

Primary Completion (Anticipated)

February 1, 2020

Study Completion (Anticipated)

March 1, 2020

Study Registration Dates

First Submitted

October 22, 2019

First Submitted That Met QC Criteria

November 3, 2019

First Posted (Actual)

November 5, 2019

Study Record Updates

Last Update Posted (Actual)

November 5, 2019

Last Update Submitted That Met QC Criteria

November 3, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201910200

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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