Diffuse GliomaPhase 2CHROMENCT06016452
A Study of Chlorophyllin for the Management of Brain Radio-necrosis in Patients With Diffuse Glioma
A Phase 2 study testing Chlorophyllin in people with Diffuse Glioma and Radionecrosis of Brain, run by Tata Memorial Centre at 1 site in India.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Diffuse Glioma, Radionecrosis of Brain, High Grade Glioma
- What is being tested?
- Chlorophyllin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 118 participants
- Where
- 1 siteIndia
- Study dates
- 13 Nov 2023to Nov 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological diagnosis of diffuse glioma.
- Radionecrosis on imaging with new neurological symptoms/ worsening of prior deficits (Stratum A) or
- without new symptoms (Stratum B).
- Karnofsky Performance Scale (KPS) ≥ 50.
Who cannot join
- No tissue diagnosis.
- KPS< 50.
- Disease progression
- Contraindications to corticosteroids.
- Altered mental status with deficits in understanding or inability to consent to the study.
- Brainstem glioma
- Indeterminate for radionecrosis vs disease progression
- Prior treatment with bevacizumab (either for disease progression or radionecrosis)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Tejpal Gupta, MD, DNB contact
India1 site, 1 recruiting
- Recruiting
Tata Memorial Hospital
Mumbai, Maharashtra, 400012
Dr Archya Dasgupta, MD
About this study
Official title: A Prospective Phase 2 Study of Chlorophyllin for the Management of Brain Radionecrosis 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.
Read more
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).
Read the detailed description
Radiotherapy (RT) forms an integral role in the multi modality management of diffuse gliomas. Radiation is indicated in low-grade gliomas with high-risk features or high-grade gliomas following maximal safe resection. Higher doses of RT can lead to symptomatic radio-necrosis (RN) in approximately 5-15% of patients, typically within the first 2-3 years of RT completion. Development of RN can lead to significant morbidity with new-onset or worsening of pre-existing neurodeficit with substantial implications on quality of life, and in extreme situations, can lead to mortality as well. The pathogenesis of RN is multi factorial, with a complex interplay of vascular-mediated damage and injury to glial cells primarily postulated through the activation of several inflammatory markers like tumor necrosis factor, interleukins, and vascular endothelial growth factor. Corticosteroids, preferably dexamethasone, form the first line of management of RN, with variable response rates ranging from 25-60%, impacted by several factors like a dose of RT and response evaluation methods (neurological/ radiographic). The response rate in our practice concurs with the reported literature with combined clinical and radiological responses seen in approximately 50% of patients from institutional experience and audit. It is important to note the long-standing use of corticosteroids comes at the cost of complications like hyperglycemia, myopathy, and increased risk of infections precluding prolonged use. Also, a proportion of patients remain refractory to steroids or turn out to be dependent on steroids, where bevacizumab (anti-angiogenic agent) can be used as second-line therapy in appropriately selected patients. However, the major disadvantages of bevacizumab remain intravenous administration requiring regular hospital visits, treatment costs, and concerns for related toxicities like hypertension, and intracranial or extracranial haemorrhage. Other agents like hyperbaric oxygen therapy, pentoxifylline, and tocopherol have been suggested in refractory radionecrosis, with questionable benefits. Sodium-copper-Chlorophyllin is a phytopharmaceutical drug obtained from the green plant pigment chlorophyll. It is a semi-synthetic mixture of sodium copper salts derived from chlorophyll. Chlorophyllin scavenges RT-induced free radicals and reactive oxygen species. It is used as a food colorant and over-the-counter in the USA, Japan, Australia, and China for many years for a variety of health benefits, including prevention of body odor in geriatric patients, enhanced wound healing, antibacterial action, prevention of cancer in the high-risk population exposed to hepatocarcinogen aflatoxin B1, treatment of fecal incontinence, etc. Studies have shown that Chlorophyllin has immunostimulatory, anti-inflammatory, and antiviral effects in addition to antioxidant and radioprotective properties. It increases the expression of a transcription factor (protein) Nrf2, improving lymphocyte survival and enabling efficient detoxification after RT exposure. Chlorophyllin also delays microtubule polymerization and slows cell division in normal cells.
- Being tested
- Chlorophyllin
- Medical subject headings
- Glioma, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChlorophyllinDrug
Also called Stratum A (Symptomatic), Stratum A (Asymptomatic)
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 coloring agent.
| Study group | Role | What they receive |
|---|---|---|
| Stratum A (Symptomatic) | Experimental | Response rates at 1 month with a combination of steroids and CHL in this study is expected to be 65% as compared to the standard 50% response with the use of dexamethasone alone. For the study with an α of 0.1 and power of 80%,50 pts will be needed to achieve the desired output. In the first stage, 22 patients will be needed for assessment and continued to stage 2 if >10 responses are seen.The stage 2 of the study will be considered successful if >29 responses are achieved using the pre-specified response assessment criteria.Considering an attrition rate of 10% from lack of follow-up and another 10% for disease progression, an estimated 60 patients will be accrued in stratum A with the purpose of achieving 50 patients with endpoints available for analysis. Receives: Drug: Chlorophyllin |
| Stratum B (Asymptomatic) | Experimental | This stratum includes pts without neurological worsening during imaging diagnosis of RN (asymptomatic RN).Approx 30% of patients continue to be neurologically/ radiologically stable or regression of imaging findings without need for further interventions (including corticosteroids).In the proposed study with the use of CHL, 45% patients are assumed to remain clinically and neurologically stable. With an α of 0.1 and power of 80%, 48 patients will be needed to achieve the desired outcome. In the first stage, 23 patients will be needed for assessment and continue to stage 2 if >6 responses are seen.
The phase 2 study will be considered successful if >18 responses are achieved using the pre-specified response assessment criteria. Further considering an attrition rate of 10% from lack of follow-up and another 10% for disease progression, an estimated 58 patients will be accrued in stratum B with the purpose of achieving 48 patients with endpoints available for analysis. Receives: Drug: Chlorophyllin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rates
Clinical-radiological
Measured: 1 month post treatment with chlorophyllin
Secondary outcomes (3)
Survival Analysis
Progression-Free Survival and Overall Survival using Kaplan-Meier survival plot.
Measured: 3 months
Health Questionnaire
EORTC QOL C -30 and (Brain module) BN-20 questionnaire. The global score and scores of subdomains will be calculated and compared with baseline.
Measured: 3 months
Response rates
Radiological response rates at 3 months using Response Assessment in Neuro-Oncology (RANO) criteria.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2023
- Study start13 Nov 2023
- Primary completionNov 2025 (estimated)
- Study completionNov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diffuse GliomaStudies of the same condition, open and under way.
- More trials run by Tata Memorial CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The proposed phase II prospective study will be split into two strata: Stratum A (symptomatic RN) and Stratum B (asymptomatic RN).
- Masking
- None (open label)
- Enrolment
- 118 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tata Memorial Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Bhabha Atomic Research Centre
- Responsible party
- Principal investigator, Dr Archya Dasgupta, Tata Memorial Centre
- Investigators
- Archya Dasgupta, MD, Principal investigator, Tata Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06016452
- Sponsor's protocol ID
- 900970
- Acronym
- CHROME
- Status last verified
- Apr 2025
- First submitted
- 10 Aug 2023
- Last updated
- 11 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dasgupta A, Sawant S, Chatterjee A, Gota V, Sahu A, Choudhari A, Bhattacharya K, Puranik A, Dev I, Moiyadi A, Shetty P, Singh V, Menon N, Epari S, Sahay A, Shah A, Bano N, Shaikh F, Jirage A, Gupta T. Study Protocol of a Prospective Phase 2 Study of Chlorophyllin for the Management of Brain Radionecrosis in Patients With Diffuse Glioma (CHROME). Cancer Med. 2025 Mar;14(5):e70657. doi: 10.1002/cam4.70657.
PubMed 40025673
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Phase 2 Study of Chlorophyllin for the Management of Brain Radionecrosis in Patients With Diffuse Glioma
- ClinicalTrials.gov ID
- NCT06016452
- Acronym / sponsor ID
- CHROME / 900970
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 118 participants (estimated)
- Lead sponsor
- Tata Memorial CentreUniversity, hospital or other
- Collaborators
- Bhabha Atomic Research Centre
- Study start
- 13 Nov 2023 (actual)
- Primary completion
- Nov 2025 (estimated)
- Study completion
- Nov 2025 (estimated)
- First posted
- 29 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Radiotherapy (RT) forms an integral role in the multi modality management of diffuse gliomas. Radiation is indicated in low-grade gliomas with high-risk features or high-grade gliomas following maximal safe resection. Higher doses of RT can lead to symptomatic radio-necrosis (RN) in approximately 5-15% of patients, typically within the first 2-3 years of RT completion. Development of RN can lead to significant morbidity with new-onset or worsening of pre-existing neurodeficit with substantial implications on quality of life, and in extreme situations, can lead to mortality as well. The pathogenesis of RN is multi factorial, with a complex interplay of vascular-mediated damage and injury to glial cells primarily postulated through the activation of several inflammatory markers like tumor necrosis factor, interleukins, and vascular endothelial growth factor. Corticosteroids, preferably dexamethasone, form the first line of management of RN, with variable response rates ranging from 25-60%, impacted by several factors like a dose of RT and response evaluation methods (neurological/ radiographic). The response rate in our practice concurs with the reported literature with combined clinical and radiological responses seen in approximately 50% of patients from institutional experience and audit. It is important to note the long-standing use of corticosteroids comes at the cost of complications like hyperglycemia, myopathy, and increased risk of infections precluding prolonged use. Also, a proportion of patients remain refractory to steroids or turn out to be dependent on steroids, where bevacizumab (anti-angiogenic agent) can be used as second-line therapy in appropriately selected patients. However, the major disadvantages of bevacizumab remain intravenous administration requiring regular hospital visits, treatment costs, and concerns for related toxicities like hypertension, and intracranial or extracranial haemorrhage. Other agents like hyperbaric oxygen therapy, pentoxifylline, and tocopherol have been suggested in refractory radionecrosis, with questionable benefits. Sodium-copper-Chlorophyllin is a phytopharmaceutical drug obtained from the green plant pigment chlorophyll. It is a semi-synthetic mixture of sodium copper salts derived from chlorophyll. Chlorophyllin scavenges RT-induced free radicals and reactive oxygen species. It is used as a food colorant and over-the-counter in the USA, Japan, Australia, and China for many years for a variety of health benefits, including prevention of body odor in geriatric patients, enhanced wound healing, antibacterial action, prevention of cancer in the high-risk population exposed to hepatocarcinogen aflatoxin B1, treatment of fecal incontinence, etc. Studies have shown that Chlorophyllin has immunostimulatory, anti-inflammatory, and antiviral effects in addition to antioxidant and radioprotective properties. It increases the expression of a transcription factor (protein) Nrf2, improving lymphocyte survival and enabling efficient detoxification after RT exposure. Chlorophyllin also delays microtubule polymerization and slows cell division in normal cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The proposed phase II prospective study will be split into two strata: Stratum A (symptomatic RN) and Stratum B (asymptomatic RN).
| Arm | Type | Receives |
|---|---|---|
| Stratum A (Symptomatic) | Experimental | Drug: ChlorophyllinResponse rates at 1 month with a combination of steroids and CHL in this study is expected to be 65% as compared to the standard 50% response with the use of dexamethasone alone. For the study with an α of 0.1 and power of 80%,50 pts will be needed to achieve the desired output. In the first stage, 22 patients will be needed for assessment and continued to stage 2 if >10 responses are seen.The stage 2 of the study will be considered successful if >29 responses are achieved using the pre-specified response assessment criteria.Considering an attrition rate of 10% from lack of follow-up and another 10% for disease progression, an estimated 60 patients will be accrued in stratum A with the purpose of achieving 50 patients with endpoints available for analysis. |
| Stratum B (Asymptomatic) | Experimental | Drug: ChlorophyllinThis stratum includes pts without neurological worsening during imaging diagnosis of RN (asymptomatic RN).Approx 30% of patients continue to be neurologically/ radiologically stable or regression of imaging findings without need for further interventions (including corticosteroids).In the proposed study with the use of CHL, 45% patients are assumed to remain clinically and neurologically stable. With an α of 0.1 and power of 80%, 48 patients will be needed to achieve the desired outcome. In the first stage, 23 patients will be needed for assessment and continue to stage 2 if >6 responses are seen. The phase 2 study will be considered successful if >18 responses are achieved using the pre-specified response assessment criteria. Further considering an attrition rate of 10% from lack of follow-up and another 10% for disease progression, an estimated 58 patients will be accrued in stratum B with the purpose of achieving 48 patients with endpoints available for analysis. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histological diagnosis of diffuse glioma.
- Radionecrosis on imaging with new neurological symptoms/ worsening of prior deficits (Stratum A) or
- without new symptoms (Stratum B).
- Karnofsky Performance Scale (KPS) ≥ 50.
Key exclusion criteria (8 listed)
- No tissue diagnosis.
- KPS< 50.
- Disease progression
- Contraindications to corticosteroids.
- Altered mental status with deficits in understanding or inability to consent to the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ChlorophyllinAlso: Stratum A (Symptomatic), Stratum A (Asymptomatic)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 coloring agent. | Drug | Stratum A (Symptomatic), Stratum B (Asymptomatic) |
Primary outcome
Response rates
Time frame: 1 month post treatment with chlorophyllin
Clinical-radiological
3 secondary outcomes
Survival Analysis
Time frame: 3 months
Health Questionnaire
Time frame: 3 months
Response rates
Time frame: 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2025.
- Derived from this study: PubMed 40025673Dasgupta A, Sawant S, Chatterjee A, Gota V, Sahu A, Choudhari A, Bhattacharya K, Puranik A, Dev I, Moiyadi A, Shetty P, Singh V, Menon N, Epari S, Sahay A, Shah A, Bano N, Shaikh F, Jirage A, Gupta T. Study Protocol of a Prospective Phase 2 Study of Chlorophyllin for the Management of Brain Radionecrosis in Patients With Diffuse Glioma (CHROME). Cancer Med. 2025 Mar;14(5):e70657. doi: 10.1002/cam4.70657.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tejpal Gupta, MD, DNB contact
Archya Dasgupta, MD principal investigator
Tata Memorial Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Chlorophyllin in people with Diffuse Glioma and Radionecrosis of Brain, run by Tata Memorial Centre at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Archya Dasgupta, MD, DNB (02224177000, archya1010@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response rates (time frame: 1 month post treatment with chlorophyllin). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06016452, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2025.