A Study of Low Dose Bevacizumab With Conventional Radiotherapy Alone in Diffuse Intrinsic Pontine Glioma (LoBULarDIPG)
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|ClinicalTrials.gov Identifier: NCT04250064|
Recruitment Status : Recruiting
First Posted : January 31, 2020
Last Update Posted : April 13, 2021
In this study, the investigators are testing improvement in survival outcomes in DIPG patients when stratified with MR perfusion score and treated with the said protocol. Newly diagnosed DIPG patients will undergo MRI perfusion study in addition to the usual MRI at diagnosis and will be stratified into hyperperfused or hypoperfused tumours.
The hyperperfused patients will receive additional low dose Bevacizumab weekly with conventional standard radiotherapy.
The hypo-perfused patients will receive ultra-low-dose radiotherapy fractionation equivalent to conventional RT biological dose.
|Condition or disease||Intervention/treatment||Phase|
|DIPG||Drug: Bevacizumab Injection Radiation: Ultra-low-dose RT||Phase 2|
In tumours like Diffuse pontine glioma (DIPG), the diagnosis itself spells a death sentence for the child affected. The current standard treatment is conventionally fractionated daily radiation treatment for 6 weeks which benefits 80-90% patients with temporary improvement in neurological function which gives survival up to 8-10 months. With research over several decades, none of the altered fractionation radiotherapy or additional chemotherapy or targeted agents has shown a significant difference in outcomes.
The investigators propose to do an MRI perfusion study in addition to usual MRI at diagnosis and stratify them into hyperperfused or hypoperfused based on the criteria from the investigator's previously published institutional experience in DIPG. The hyperperfused patients will receive additional low dose a drug called Bevacizumab weekly with conventional standard radiotherapy. It is hypothesized that low dose Bevacizumab will decrease hypoxia and improve the efficacy of conventional radiotherapy and in turn improve outcomes.
The hypo-perfused patients will receive ultra-low-dose radiotherapy fractionation equivalent to conventional RT biological dose. As it is assumed that hypoperfused tumours are radioresistant, the investigator hypothesis that the ultra-low dose radiotherapy may overcome that radioresistance as seen in GBM adult patients and may improve outcomes.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Study of Low Dose Bevacizumab With Conventional Radiotherapy Alone in Diffuse Intrinsic Pontine Glioma|
|Actual Study Start Date :||February 4, 2020|
|Estimated Primary Completion Date :||February 2023|
|Estimated Study Completion Date :||February 2023|
Experimental: Concurrent low-dose Bevacizumab
Low-dose concurrent Bevacizumab with standard radiotherapy
Drug: Bevacizumab Injection
Additional concurrent low-dose Bevacizumab with standard EBRT
Other Name: Concurrent low-dose Bevacizumab
Experimental: Ultra-low-dose RT
Radiation: Ultra-low-dose RT
Ultra-low-dose EBRT instead of standard dose RT
- Overall Survival [ Time Frame: median of 12 months from diagnosis ]Survival for the total enrolled patient population will calculated at the median follow up 12 months. This will be compared with historical data from TMH, international DIPG registry and SIOP DIPG registry for 12-month OS as 35%.
- Progression-free survival [ Time Frame: 6 months, 12 months, 18 months from diagnosis ]Progression-free survival: at 6 months, 12 months, 18 months will be recorded for overall cohort and each arm separately at first progression only. For the purpose of the study, any patient with two or more new clinical signs of neurological deterioration in accordance with classical DIPG diagnosis with radiological progression of disease from any previous available imaging will be called progression.
- Adverse events [ Time Frame: From the time of intervention beginning, through the course of intervention, at the end of intervention and follow up 3 monthly to the date of precluding progression, or last known follow-up date, assessed for up to 2 years ]The documentation of highest grade of toxicity as per CTCAE v 4 and RTOG radiation toxicity.
- Steroid Use [ Time Frame: From the time of intervention beginning, through the course of intervention, at the end of intervention and follow up 3 monthly to the date of precluding progression, or last known follow-up date, assessed for up to 2 years ]Total duration of steroid use will be recorded
- Pattern of relapse [ Time Frame: from the date of enrollment on study to the last known follow-up date, assessed for up to 2 years ]local versus disseminated progression will be documented for each arm and overall cohort for the patients with available MRI at progression.
- Overall survival [ Time Frame: 6, 12 month and 18 months. ]Overall survival in each arm as well as for overall cohort will be recorded
- Compliance [ Time Frame: From the time of intervention beginning, through the course of intervention, till the planned intervention is completed to maximum of 10 weeks from beginning , which ever is earlier. ]Treatment intervention abandonment rates: number of patients not completing the planned intervention/treatment.
- Inconvenience rates [ Time Frame: From the time of intervention beginning, through the course of intervention, till the end of intervention or maximum of upto 10 weeks, which ever is earlier. ]average number of hours spent in hospital per day during the intervention phase.
- Quality of Life scores [ Time Frame: From date of accrual until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months ]The Qol scores will be calculated as per the routine OPD based collection of Health using utilities index (40 item standard questionnaire) and/or PedQol interviewer based scores.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04250064
|Contact: Rahul Krishnatry, Dr||022-24177000 ext firstname.lastname@example.org|
|Tata Memorial Hospital||Recruiting|
|Mumbai, Maharashtra, India, 400012|
|Contact: Dr Rahul Krishnatry, MD 022-24177000 ext 6023 email@example.com|
|Principal Investigator:||Rahul Krishnatry, Dr||Tata Memorial Hospital|