Clinical trial NCT04152681: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Radiation Injuries
Keywords: Apatinib
Radiation-induced brain injury
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2019-11-05
Enrollment: 36
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall efficacy rate
timeFrame: 4 weeks
Secondary outcomes:
measure: Change of brain necrosis
timeFrame: 4 weeks
measure: Change in neurological function
timeFrame: 4 weeks
measure: Change in the quality of life
timeFrame: 4 weeks
measure: Change of white matter structural connectivity
timeFrame: 4 weeks
measure: Change in cognitive function
timeFrame: 4 weeks
measure: Change in pain intensity
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Guanzhou
country: China
facility: Yamei Tang
state: Guangdong
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Yamei Tang, M.D., Ph.D.
role: STUDY_DIRECTOR
References: