Clinical trial NCT03208413: The Therapeutic Effect of Thalidomide in RI
Official title: The Effect of Thalidomide in Radiation-induced Brain Injury（RI）: a Phase II Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Radiation Injuries
Keywords: thalidomide
radiation-induced brain injury
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2017-07-05
Enrollment: 58
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Purpose: This phase II clinical trial aims to evaluate the indications, therapeutic effects and side effects of thalidomide in radiation-induced brain injury.

Further study details as provided by Sun Yat-sen Memorial Hospital, Sun Yat-sen University / Yameitang.

Primary outcome measure: The primary endpoint is the brain injury remission at week 15. In brief, the brain lesion will be evaluated by using brain MRI scan before and after thalidomide regimen. The clinical efficacy is defined as ≥ 25% reduction in brain edema volume on FLAIR images at week 15, as compared with that before thalidomide usage.

Detailed description: There is no acknowledged and effective standard treatment for radiation-induced brain injury (RI). Glucocorticoids and bevacizumab during acute period are optional ways to reduce the brain edema. However, glucocorticoids and bevacizumab are unsuitable or ineffective for some patients, especially in the early stage of RI. The investigators supposed that angiogenesis might play a key role in the pathogenesis of RI, and that thalidomide, as an antiangiogenic drug, would reduce immature angiogenesis and improve vessel maturation in RI.

Primary objectives: This phase II clinical trial aims to evaluate the indications, therapeutic effects and safety of thalidomide in radiation-induced brain injury.

OUTLINE: This is a phase II, open-label, single arm clinical trial. Patients are enrolled and administrated with thalidomide. Thalidomide is supplied as 25 mg per pill to be taken by mouth.

Arm І: Patients receive thalidomide with a dosage of 25 mg at bedtime daily one week (days 1-7), then 50 mg at bedtime daily for one week (days 8-14), then 75 mg at bedtime daily for one week (days 15-21), then 100 mg at bedtime daily for 12 weeks (days 22-105), in the absence of unacceptable toxicity or severe deterioration.

Eligibility criteria: Inclusion Criteria

* Prior irradiation \>/= 12 months prior to study entry.
* Radiographic evidence to support the diagnosis of radiation-induced brain injury without tumor recurrence.
* Age\>/= 35 years.
* Contraindication to glucocorticoids and bevacizumab treatment due to history or high risk of severe adverse effects, or non-effective response to glucocorticoids and bevacizumab treatment in 12 months prior to study entry.
* Estimated life expectancy must be greater than 12 months.
* Routine laboratory studies: bilirubin \</=1.0 \* upper limits of normal (ULN); aspartate aminotransferase (AST or SGOT) or alanine aminotransferase (ALT)\< 1.0 \* ULN; creatinine \<1.0 \* ULN; white-cell count \>/= 4,000 per cubic millimeter; neutrophils count \>/=1500 per cubic millimeter platelets \>/= 100,000 per cubic millimeter; Hb \>/=110 gram per millilitres; PT, APTT, INR in a normal range.
* Ability to understand and willingness to sign a written informed consent document, or constant caregivers who well understand and willingness to sign a written informed consent document.

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 need surgery;
* History of psychiatric diseases before radiotherapy;
* History of seizures;
* History of arteriosclerotic cardiovascular diseases (ASCVD), e.g. stroke, myocardial infaction, unstable angina, within 6 months;
* New York Heart Association Grade II or greater congestive heart failure;
* Serious and inadequately controlled cardiac arrhythmia;
* Significant vascular disease, e.g. moderate or severe carotid stenosis, aortic aneurysm, 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 in liver and renal function;
* Active tuberculosis;
* Transplanted organs;
* Human immunodeficiency virus;
* Participation in other experimental studies.

Primary outcomes:
measure: the brain injury remission
timeFrame: Week 15
Secondary outcomes:
measure: improvement of quality of life
timeFrame: Week 15
measure: improvement of neurological function
timeFrame: Week 15
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Cancer canter of Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
state: Guangdong
city: Guanzhou
country: China
facility: Guangzhou Huiai Hospital
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: