A Study of Low Dose Bevacizumab With Conventional Radiotherapy Alone in Diffuse Intrinsic Pontine Glioma (LoBULarDIPG)

November 20, 2023 updated by: Tata Memorial Centre

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • India
    • Maharashtra
      • Mumbai, Maharashtra, India, 400012
        • Recruiting
        • Tata Memorial Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Tumour Diagnosis: Newly diagnosed non-disseminated treatment naïve DIPG by classic clinical AND radiographic finding.
  2. Age: Patient must be 3 to 18 years of age at the time of diagnosis.
  3. Performance Score: KPS > 12 y/o >/= 50 or LPS for < 12y >/= 50 assessed at enrollment.

  4. Participants must have normal organ and marrow function as defined below within two weeks prior to enrollment:

    1. Hematological: Absolute neutrophil count > 1,000/mcL, Platelets> 100,000/mcL (transfusion independent), HB > 8gm/dL (can be transfused)
    2. 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.
    3. 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.
    4. Normal coagulation profile
  5. 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.
  6. No contra-indication for GA for MRI
  7. Would not need GA for RT in the hypofractionated subgroup (due to logistics).
  8. 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,

  1. 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
  2. Patients with uncontrolled systemic hypertension/ Proteinuria with a urine protein (albumin)/creatinine ratio of ≥1.0.
  3. 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.
  4. Allergies: Patients with a history of allergic reaction to Chinese hamster ovary cell products, or other recombinant human antibodies.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Concurrent low-dose Bevacizumab
Low-dose concurrent Bevacizumab with standard radiotherapy
Drug: Bevacizumab Injection
Additional concurrent low-dose Bevacizumab with standard EBRT
Other Names:
  • Concurrent low-dose Bevacizumab
Experimental: Ultra-low-dose RT
Radiation: Ultra-low-dose RT
Ultra-low-dose EBRT instead of standard dose RT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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%.
median of 12 months from diagnosis

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 months, 12 months, 18 months from diagnosis
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.
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
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
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
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.
from the date of enrollment on study to the last known follow-up date, assessed for up to 2 years
Overall survival
Time Frame: 6, 12 month and 18 months.
Overall survival in each arm as well as for overall cohort will be recorded
6, 12 month and 18 months.
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.
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.
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.
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.
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.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tata Memorial Centre

Investigators

  • Principal Investigator: Rahul Krishnatry, Dr, Tata Memorial Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 4, 2020

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

January 7, 2020

First Submitted That Met QC Criteria

January 30, 2020

First Posted (Actual)

January 31, 2020

Study Record Updates

Last Update Posted (Actual)

November 22, 2023

Last Update Submitted That Met QC Criteria

November 20, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3201

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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