Clinical Research Directory

Corticodependent or Corticoresistant Brain Radionecrosis After Radiotherapy for Brain Metastases

Brain metastases (BM) afflict a significant portion of cancer patients, ranging from 10% to 50%, leading to debilitating symptoms and diminished quality of life, thereby impacting overall survival. Treatment options typically include surgery, stereotactic radiosurgery (SRS), and whole brain radiotherapy (WBRT). SRS has emerged as the preferred focal treatment due to its efficacy, delivering ablative doses with notable overall survival benefits, especially for single BM or postoperative cases, while being less invasive than neurosurgery and capable of addressing inoperable sites and multiple lesions. Contrastingly, WBRT is now reserved for select cases with multiple BMs ineligible for SRS, owing to its lower rate of neurocognitive toxicities and high local control rates at one year. Despite its advantages, SRS can engender late side effects, with cerebral radio necrosis (RN) being the most common, occurring in approximately 10% of patients treated. The exact pathophysiology of RN remains unclear but is thought to involve vascular injury, immune-mediated mechanisms, and direct neuronal effects, culminating in radiological changes or symptomatic manifestations necessitating treatment. Corticosteroids are the mainstay therapy, albeit with associated side effects and instances of cortico-resistance or cortico-dependence. Bevacizumab, an anti-VEGF agent, has shown promise in small studies but awaits validation in larger trials. Consequently, a randomized phase III trial seeks to evaluate the efficacy of adding bevacizumab to standard corticosteroid therapy in patients with symptomatic RN. The trial aims to determine if this combination therapy yields superior symptomatic improvement compared to corticosteroids alone. RN will be diagnosed using multimodal imaging, and the primary objective is to assess the efficacy of bevacizumab in reducing corticosteroid usage and neurological symptoms associated with RN at three months. Secondary endpoints include toxicities, quality of life, imaging changes, and response duration. Additionally, an ancillary study will explore correlations between initial imaging parameters and treatment response, as well as changes in biological parameters with bevacizumab therapy.

A Study of Chlorophyllin for the Management of Brain Radio-necrosis in Patients With Diffuse Glioma

Diffuse gliomas are common tumors involving the brain. They are usually treated by surgery followed by radiation and chemotherapy. Radiotherapy is used for the treatment of brain tumors which causes damage to the tumor cells. However, radiotherapy can also affect the surrounding healthy cells in the brain, causing inflammation and swelling in the region, which is known as radio necrosis (RN). This is considered a late side effect of radiation and is seen in 10-25% of patients treated with radiation for brain tumors. Sometimes, radionecrosis can be detected on routine imaging during follow-up without new symptoms (asymptomaticRN). At the same time, in some patients, it can give rise to new symptoms like headaches, weakness, seizures,etc (symptomatic RN). The standard treatment of RN includes steroid medicines called dexamethasone, which is helpful in a proportion of patients. This is a prospective phase 2 study. This study is being conducted to investigate the ability of the drug Chlorophyllin in the treatment of radionecrosis. Chlorophyllin is a water-soluble compound obtained from the green plant pigment called chlorophyll. It has been shown to have anti-cancer, anti-bacterial, anti-viral, anti-inflammatory, and antioxidant properties. It is also used as an oral formulation and is an over-the-counter drug in various countries, and also as a food colouring agent. This is the first time chlorophyllin will be used in the setting of brain radionecrosis. Our primary aim of the study is to assess whether CHL will improve the clinical-radiological response rates. This study will be conducted on a population of 118 patients for a duration of 3 months. The total study duration is 2 years. The study is funded by Bhabha Atomic Research Centre (BARC).

FET-PET-Guided Management of Pseudoprogression in Glioblastoma

The goal of this diagnostic randomised clinical trial is to determine, in glioblastoma patients with diagnostic uncertainty between pseudoprogression and tumor progression on follow-up MRI after chemoradiation, the added value of a direct \[¹⁸F\] FET-PET scan for clinical management. The main questions it aims to answer are: * Does the clinical management guided by an additional FET-PET scan leads to fewer unnecessary interventions, compared with management based on MRI only? * Does the clinical management guided by an additional FET-PET scan leads to better health-related quality of life after 12 weeks, compared with management based on MRI only? * Does the clinical management guided by an additional FET-PET scan leads to reduced net healthcare costs, compared with management based on MRI only? Researchers will compare the investigational arm, where clinical management is based on the index MRI scan and an additional FET-PET scan, with the control arm, where clinical management is based solely on the index MRI scan, to investigate the added value of the FET PET scan for clinical management. Participants in the investigational arm will undergo the FET PET scan. All participants will complete health-related quality of life questionnaires at four different timepoints.