Study Protocol of a Prospective Phase 2 Study of Chlorophyllin for the Management of Brain Radionecrosis in Patients With Diffuse Glioma (CHROME)

ABSTRACT Introduction 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 patien...

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Main Authors: Archya Dasgupta, Saranga Sawant, Abhishek Chatterjee, Vikram Gota, Arpita Sahu, Amitkumar Choudhari, Kajari Bhattacharya, Ameya Puranik, Indraja Dev, Aliasgar Moiyadi, Prakash Shetty, Vikas Singh, Nandini Menon, Sridhar Epari, Ayushi Sahay, Aekta Shah, Nazia Bano, Farnaz Shaikh, Aabha Jirage, Tejpal Gupta
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.70657
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author Archya Dasgupta
Saranga Sawant
Abhishek Chatterjee
Vikram Gota
Arpita Sahu
Amitkumar Choudhari
Kajari Bhattacharya
Ameya Puranik
Indraja Dev
Aliasgar Moiyadi
Prakash Shetty
Vikas Singh
Nandini Menon
Sridhar Epari
Ayushi Sahay
Aekta Shah
Nazia Bano
Farnaz Shaikh
Aabha Jirage
Tejpal Gupta
author_facet Archya Dasgupta
Saranga Sawant
Abhishek Chatterjee
Vikram Gota
Arpita Sahu
Amitkumar Choudhari
Kajari Bhattacharya
Ameya Puranik
Indraja Dev
Aliasgar Moiyadi
Prakash Shetty
Vikas Singh
Nandini Menon
Sridhar Epari
Ayushi Sahay
Aekta Shah
Nazia Bano
Farnaz Shaikh
Aabha Jirage
Tejpal Gupta
author_sort Archya Dasgupta
collection DOAJ
description ABSTRACT Introduction 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. Methods 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. Discussion 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. Trial Registration: Clinical Trial Registry India (CTRI): CTRI/2023/08/056166; ClinicalTrials.gov: NCT06016452
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publisher Wiley
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series Cancer Medicine
spelling doaj-art-bd470ca0bf80467c9909ee86a03b14382025-08-20T02:52:44ZengWileyCancer Medicine2045-76342025-03-01145n/an/a10.1002/cam4.70657Study Protocol of a Prospective Phase 2 Study of Chlorophyllin for the Management of Brain Radionecrosis in Patients With Diffuse Glioma (CHROME)Archya Dasgupta0Saranga Sawant1Abhishek Chatterjee2Vikram Gota3Arpita Sahu4Amitkumar Choudhari5Kajari Bhattacharya6Ameya Puranik7Indraja Dev8Aliasgar Moiyadi9Prakash Shetty10Vikas Singh11Nandini Menon12Sridhar Epari13Ayushi Sahay14Aekta Shah15Nazia Bano16Farnaz Shaikh17Aabha Jirage18Tejpal Gupta19Department of Radiation Oncology Tata Memorial Centre Mumbai IndiaHomi Bhabha National Institute (HBNI) Mumbai IndiaDepartment of Radiation Oncology Tata Memorial Centre Mumbai IndiaHomi Bhabha National Institute (HBNI) Mumbai IndiaHomi Bhabha National Institute (HBNI) Mumbai IndiaHomi Bhabha National Institute (HBNI) Mumbai IndiaHomi Bhabha National Institute (HBNI) Mumbai IndiaHomi Bhabha National Institute (HBNI) Mumbai IndiaHomi Bhabha National Institute (HBNI) Mumbai IndiaHomi Bhabha National Institute (HBNI) Mumbai IndiaHomi Bhabha National Institute (HBNI) Mumbai IndiaHomi Bhabha National Institute (HBNI) Mumbai IndiaHomi Bhabha National Institute (HBNI) Mumbai IndiaHomi Bhabha National Institute (HBNI) Mumbai IndiaHomi Bhabha National Institute (HBNI) Mumbai IndiaHomi Bhabha National Institute (HBNI) Mumbai IndiaDepartment of Radiation Oncology Tata Memorial Centre Mumbai IndiaDepartment of Radiation Oncology Tata Memorial Centre Mumbai IndiaDepartment of Radiation Oncology Tata Memorial Centre Mumbai IndiaDepartment of Radiation Oncology Tata Memorial Centre Mumbai IndiaABSTRACT Introduction 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. Methods 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. Discussion 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. Trial Registration: Clinical Trial Registry India (CTRI): CTRI/2023/08/056166; ClinicalTrials.gov: NCT06016452https://doi.org/10.1002/cam4.70657chlorophyllindiffuse gliomaglioblastomahigh‐grade gliomaradionecrosis
spellingShingle Archya Dasgupta
Saranga Sawant
Abhishek Chatterjee
Vikram Gota
Arpita Sahu
Amitkumar Choudhari
Kajari Bhattacharya
Ameya Puranik
Indraja Dev
Aliasgar Moiyadi
Prakash Shetty
Vikas Singh
Nandini Menon
Sridhar Epari
Ayushi Sahay
Aekta Shah
Nazia Bano
Farnaz Shaikh
Aabha Jirage
Tejpal Gupta
Study Protocol of a Prospective Phase 2 Study of Chlorophyllin for the Management of Brain Radionecrosis in Patients With Diffuse Glioma (CHROME)
Cancer Medicine
chlorophyllin
diffuse glioma
glioblastoma
high‐grade glioma
radionecrosis
title Study Protocol of a Prospective Phase 2 Study of Chlorophyllin for the Management of Brain Radionecrosis in Patients With Diffuse Glioma (CHROME)
title_full Study Protocol of a Prospective Phase 2 Study of Chlorophyllin for the Management of Brain Radionecrosis in Patients With Diffuse Glioma (CHROME)
title_fullStr Study Protocol of a Prospective Phase 2 Study of Chlorophyllin for the Management of Brain Radionecrosis in Patients With Diffuse Glioma (CHROME)
title_full_unstemmed Study Protocol of a Prospective Phase 2 Study of Chlorophyllin for the Management of Brain Radionecrosis in Patients With Diffuse Glioma (CHROME)
title_short Study Protocol of a Prospective Phase 2 Study of Chlorophyllin for the Management of Brain Radionecrosis in Patients With Diffuse Glioma (CHROME)
title_sort study protocol of a prospective phase 2 study of chlorophyllin for the management of brain radionecrosis in patients with diffuse glioma chrome
topic chlorophyllin
diffuse glioma
glioblastoma
high‐grade glioma
radionecrosis
url https://doi.org/10.1002/cam4.70657
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