Dasgupta Archya, Sawant Saranga, Chatterjee Abhishek, Gota Vikram, Sahu Arpita, Choudhari Amitkumar, Bhattacharya Kajari, Puranik Ameya, Dev Indraja, Moiyadi Aliasgar, Shetty Prakash, Singh Vikas, Menon Nandini, Epari Sridhar, Sahay Ayushi, Shah Aekta, Bano Nazia, Shaikh Farnaz, Jirage Aabha, Gupta Tejpal
Department of Radiation Oncology, Tata Memorial Centre, Mumbai, India.
Homi Bhabha National Institute (HBNI), Mumbai, India.
Cancer Med. 2025 Mar;14(5):e70657. doi: 10.1002/cam4.70657.
Chlorophyllin (CHL) effectively decreases the side effects of radiotherapy (RT) by scavenging radiation-induced free radicals and reactive oxygen species in preclinical trials. This study aims to assess the efficacy of oral CHL for the treatment of brain radionecrosis in patients with diffuse glioma.
This is a phase 2 trial prospective, interventional study. Adults (> 18 years) with a histological diagnosis of diffuse glioma developing radionecrosis will be eligible for the study. Radionecrosis will be identified using standard imaging protocols with magnetic resonance imaging (MRI) with or without positron emission tomography (PET). Patients will be accrued in two strata: symptomatic (stratum A) and asymptomatic (stratum B). Chlorophyllin will be prescribed to all patients using a morning oral dose of 750 mg before breakfast for 3 months. In addition, participants in stratum A will be given a tapering dose of dexamethasone for 1 month, while stratum B will not be receiving any steroids. Imaging with an MRI brain protocol and PET scan will be planned at 1 month and MRI at 3 months after starting CHL. The primary endpoint is the clinical-radiological response at 1 month. Secondary endpoints include response at 3 months, biological responses, survival analysis, and quality-of-life scores. The total sample size is 118 (60 and 58 in stratum A and B, respectively), with one interim analysis planned.
Radionecrosis leads to significant morbidity and is usually treated with corticosteroids, which can lead to several side effects from both acute and long-term use. Refractory radionecrosis requires treatment with bevacizumab or surgical resection. Chlorophyllin is a cheap, safe, and readily available phytopharmaceutical drug, which is being investigated in the phase 2 study and, if proven effective, can be considered an alternative for treating radionecrosis.
Clinical Trial Registry India (CTRI): CTRI/2023/08/056166; ClinicalTrials.gov: NCT06016452.
在临床前试验中，叶绿酸（CHL）通过清除辐射诱导的自由基和活性氧，有效降低了放射治疗（RT）的副作用。本研究旨在评估口服CHL治疗弥漫性胶质瘤患者脑放射性坏死的疗效。
这是一项2期前瞻性干预研究。组织学诊断为弥漫性胶质瘤并发放射性坏死的成年人（>18岁）符合本研究条件。将使用标准成像方案，通过磁共振成像（MRI）（有无正电子发射断层扫描（PET））来识别放射性坏死。患者将分为两个分层：有症状（A层）和无症状（B层）。所有患者早餐前口服750mg叶绿酸，持续3个月。此外，A层参与者将接受为期1个月的逐渐减量的地塞米松治疗，而B层将不接受任何类固醇治疗。在开始使用CHL后1个月计划进行脑部MRI协议成像和PET扫描，3个月时进行MRI扫描。主要终点是1个月时的临床放射学反应。次要终点包括3个月时的反应、生物学反应、生存分析和生活质量评分。总样本量为118例（A层和B层分别为60例和58例），计划进行一次中期分析。
放射性坏死会导致严重的发病率，通常用皮质类固醇治疗，这可能会导致急性和长期使用的多种副作用。难治性放射性坏死需要用贝伐单抗或手术切除治疗。叶绿酸是一种廉价、安全且易于获得的植物药，正在进行2期研究，如果被证明有效，可以被视为治疗放射性坏死的替代药物。
印度临床试验注册中心（CTRI）：CTRI/2023/08/056166；美国国立医学图书馆临床试验数据库（ClinicalTrials.gov）：NCT06016452。
