Back to resultsA Study of Low Dose Bevacizumab With Conventional Radiotherapy Alone in Diffuse Intrinsic Pontine Glioma (LoBULarDIPG)
Primary Purpose
DIPG
Status
Recruiting
Phase
Phase 2
Locations
India
Study Type
Interventional
Intervention
Bevacizumab Injection
Ultra-low-dose RT
Sponsored by
About this trial
This is an interventional treatment trial for DIPG
Eligibility Criteria
Inclusion Criteria:
- Tumour Diagnosis: Newly diagnosed non-disseminated treatment naïve DIPG by classic clinical AND radiographic finding.
- Age: Patient must be 3 to 18 years of age at the time of diagnosis.
- Performance Score: KPS > 12 y/o >/= 50 or LPS for < 12y >/= 50 assessed at enrollment.
Participants must have normal organ and marrow function as defined below within two weeks prior to enrollment:
- Hematological: Absolute neutrophil count > 1,000/mcL, Platelets> 100,000/mcL (transfusion independent), HB > 8gm/dL (can be transfused)
- Hepatic: Total bilirubin < 1.5 times the upper limit of normal; alanine aminotransferase [SGPT (ALT)] and aspartate aminotransferase [SGOT (AST)] < 5 times the institutional upper limit of normal.
- Renal: Serum creatinine which is less than 1.5x the upper limit of institutional normal for age or Glomerular Filtration Rate (GFR) > 70 ml/min/1.73m2.; The absence of clinically significant proteinuria as defined by a screening early morning urine (first sample) dipstick urinalysis of < 2.
- Normal coagulation profile
- Post-Biopsy patients allowed, but should not have evidence of haemorrhage greater than 0.5cm intracranially and should satisfy this criterion within two to four weeks of biopsy to start treatment in Arm 1 if designated as per perfusion study along with satisfying other criteria as applicable. For arm 2, there will be no restriction other than the usual criteria.
- No contra-indication for GA for MRI
- Would not need GA for RT in the hypofractionated subgroup (due to logistics).
- Ability to understand and the willingness to sign a written informed consent document by the parent or guardian and assent by the child as applicable and as per institutional policy.
Exclusion Criteria:
Other than those mentioned above,
- Surgical Procedures: Patients who have had major surgery should not receive the first dose of BVZ until 28 days after major surgery or Serious or Non-Healing Wounds
- Patients with uncontrolled systemic hypertension/ Proteinuria with a urine protein (albumin)/creatinine ratio of ≥1.0.
- Thrombosis: Patients must not have been previously diagnosed with a deep venous or arterial thrombosis (including pulmonary embolism), and must not have a known thrombophilic condition.
- Allergies: Patients with a history of allergic reaction to Chinese hamster ovary cell products, or other recombinant human antibodies.
Sites / Locations
- Tata Memorial HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Concurrent low-dose Bevacizumab
Ultra-low-dose RT
Arm Description
Low-dose concurrent Bevacizumab with standard radiotherapy
Ultra-low-dose RT
Outcomes
Primary Outcome Measures
Overall Survival
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%.
Secondary Outcome Measures
Progression-free survival
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
The documentation of highest grade of toxicity as per CTCAE v 4 and RTOG radiation toxicity.
Steroid Use
Total duration of steroid use will be recorded
Pattern of relapse
local versus disseminated progression will be documented for each arm and overall cohort for the patients with available MRI at progression.
Overall survival
Overall survival in each arm as well as for overall cohort will be recorded
Compliance
Treatment intervention abandonment rates: number of patients not completing the planned intervention/treatment.
Inconvenience rates
average number of hours spent in hospital per day during the intervention phase.
Quality of Life scores
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04250064
Brief Title
A Study of Low Dose Bevacizumab With Conventional Radiotherapy Alone in Diffuse Intrinsic Pontine Glioma
Acronym
LoBULarDIPG
Official Title
A Study of Low Dose Bevacizumab With Conventional Radiotherapy Alone in Diffuse Intrinsic Pontine Glioma
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 4, 2020 (Actual)
Primary Completion Date
February 2023 (Anticipated)
Study Completion Date
February 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tata Memorial Centre
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
DIPG
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Concurrent low-dose Bevacizumab
Arm Type
Experimental
Arm Description
Low-dose concurrent Bevacizumab with standard radiotherapy
Arm Title
Ultra-low-dose RT
Arm Type
Experimental
Arm Description
Ultra-low-dose RT
Intervention Type
Drug
Intervention Name(s)
Bevacizumab Injection
Other Intervention Name(s)
Concurrent low-dose Bevacizumab
Intervention Description
Additional concurrent low-dose Bevacizumab with standard EBRT
Intervention Type
Radiation
Intervention Name(s)
Ultra-low-dose RT
Intervention Description
Ultra-low-dose EBRT instead of standard dose RT
Primary Outcome Measure Information:
Title
Overall Survival
Description
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%.
Time Frame
median of 12 months from diagnosis
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
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.
Time Frame
6 months, 12 months, 18 months from diagnosis
Title
Adverse events
Description
The documentation of highest grade of toxicity as per CTCAE v 4 and RTOG radiation toxicity.
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
Title
Steroid Use
Description
Total duration of steroid use will be recorded
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
Title
Pattern of relapse
Description
local versus disseminated progression will be documented for each arm and overall cohort for the patients with available MRI at progression.
Time Frame
from the date of enrollment on study to the last known follow-up date, assessed for up to 2 years
Title
Overall survival
Description
Overall survival in each arm as well as for overall cohort will be recorded
Time Frame
6, 12 month and 18 months.
Title
Compliance
Description
Treatment intervention abandonment rates: number of patients not completing the planned intervention/treatment.
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.
Title
Inconvenience rates
Description
average number of hours spent in hospital per day during the intervention phase.
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.
Title
Quality of Life scores
Description
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.
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Tumour Diagnosis: Newly diagnosed non-disseminated treatment naïve DIPG by classic clinical AND radiographic finding.
Age: Patient must be 3 to 18 years of age at the time of diagnosis.
Performance Score: KPS > 12 y/o >/= 50 or LPS for < 12y >/= 50 assessed at enrollment.
Participants must have normal organ and marrow function as defined below within two weeks prior to enrollment:
Hematological: Absolute neutrophil count > 1,000/mcL, Platelets> 100,000/mcL (transfusion independent), HB > 8gm/dL (can be transfused)
Hepatic: Total bilirubin < 1.5 times the upper limit of normal; alanine aminotransferase [SGPT (ALT)] and aspartate aminotransferase [SGOT (AST)] < 5 times the institutional upper limit of normal.
Renal: Serum creatinine which is less than 1.5x the upper limit of institutional normal for age or Glomerular Filtration Rate (GFR) > 70 ml/min/1.73m2.; The absence of clinically significant proteinuria as defined by a screening early morning urine (first sample) dipstick urinalysis of < 2.
Normal coagulation profile
Post-Biopsy patients allowed, but should not have evidence of haemorrhage greater than 0.5cm intracranially and should satisfy this criterion within two to four weeks of biopsy to start treatment in Arm 1 if designated as per perfusion study along with satisfying other criteria as applicable. For arm 2, there will be no restriction other than the usual criteria.
No contra-indication for GA for MRI
Would not need GA for RT in the hypofractionated subgroup (due to logistics).
Ability to understand and the willingness to sign a written informed consent document by the parent or guardian and assent by the child as applicable and as per institutional policy.
Exclusion Criteria:
Other than those mentioned above,
Surgical Procedures: Patients who have had major surgery should not receive the first dose of BVZ until 28 days after major surgery or Serious or Non-Healing Wounds
Patients with uncontrolled systemic hypertension/ Proteinuria with a urine protein (albumin)/creatinine ratio of ≥1.0.
Thrombosis: Patients must not have been previously diagnosed with a deep venous or arterial thrombosis (including pulmonary embolism), and must not have a known thrombophilic condition.
Allergies: Patients with a history of allergic reaction to Chinese hamster ovary cell products, or other recombinant human antibodies.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rahul Krishnatry, Dr
Phone
022-24177000
Ext
7028
Email
krishnatry@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rahul Krishnatry, Dr
Organizational Affiliation
Tata Memorial Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tata Memorial Hospital
City
Mumbai
State/Province
Maharashtra
ZIP/Postal Code
400012
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr Rahul Krishnatry, MD
Phone
022-24177000
Ext
6023
Email
krishnatry@gmail.com
12. IPD Sharing Statement
Learn more about this trial
A Study of Low Dose Bevacizumab With Conventional Radiotherapy Alone in Diffuse Intrinsic Pontine Glioma
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