Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Mar;14(5):e70657.
doi: 10.1002/cam4.70657.

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

Archya Dasgupta  1   2 , Saranga Sawant  2   3 , Abhishek Chatterjee  1   2 , Vikram Gota  2   4 , Arpita Sahu  2   5 , Amitkumar Choudhari  2   5 , Kajari Bhattacharya  2   5 , Ameya Puranik  2   6 , Indraja Dev  2   6 , Aliasgar Moiyadi  2   7 , Prakash Shetty  2   7 , Vikas Singh  2   7 , Nandini Menon  2   8 , Sridhar Epari  2   9 , Ayushi Sahay  2   9 , Aekta Shah  2   9 , Nazia Bano  1   3 , Farnaz Shaikh  1   3 , Aabha Jirage  1 , Tejpal Gupta  1   2
Affiliations

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

Archya Dasgupta et al. Cancer Med. 2025 Mar.

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.

Keywords: chlorophyllin; diffuse glioma; glioblastoma; high‐grade glioma; radionecrosis.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Radiological findings for a patient with radionecrosis. (A, B) show the presence of an enhancing rim with a central necrotic core along the right periventricular region. (C) is the corresponding T2‐weighted image showing significant edema. (D) is the F‐DOPA PET showing low‐grade avidity of the lesion.
FIGURE 2
FIGURE 2
Schematic representation of the conduct of the study.
See this image and copyright information in PMC

References

    1. Stupp R., Mason W. P., van den Bent M. J., et al., “Radiotherapy Plus Concomitant and Adjuvant Temozolomide for Glioblastoma,” New England Journal of Medicine 352 (2005): 987–996. - PubMed
    1. Weller M., van den Bent M., Preusser M., et al., “EANO Guidelines on the Diagnosis and Treatment of Diffuse Gliomas of Adulthood,” Nature Reviews. Clinical Oncology 18, no. 3 (2021): 170–186, 10.1038/s41571-020-00447-z. - DOI - PMC - PubMed
    1. Mohile N. A., Messersmith H., Gatson N. T., et al., “Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO‐SNO Guideline,” Journal of Clinical Oncology 40 (2022): 403–426. - PubMed
    1. Miyatake S.‐I., Nonoguchi N., Furuse M., et al., “Pathophysiology, Diagnosis, and Treatment of Radiation Necrosis in the Brain,” Neurologia Medico‐Chirurgica (Tokyo) 55 (2015): 50–59. - PMC - PubMed
    1. Zikou A., Sioka C., Alexiou G. A., Fotopoulos A., Voulgaris S., and Argyropoulou M. I., “Radiation Necrosis, Pseudoprogression, Pseudoresponse, and Tumor Recurrence: Imaging Challenges for the Evaluation of Treated Gliomas,” Contrast Media & Molecular Imaging 2018 (2018): 6828396. - PMC - PubMed

Publication types

MeSH terms

Associated data