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

NCT ID: NCT04250064

Last Updated: 2025-04-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-04
• Study Completion Date: 2029-12-31

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.

Conditions

DIPG

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Concurrent low-dose Bevacizumab

Low-dose concurrent Bevacizumab with standard radiotherapy

Group Type: EXPERIMENTAL

Bevacizumab Injection

Intervention Type: DRUG

Additional concurrent low-dose Bevacizumab with standard EBRT

Ultra-low-dose RT

Ultra-low-dose RT

Group Type: EXPERIMENTAL

Ultra-low-dose RT

Intervention Type: RADIATION

Ultra-low-dose EBRT instead of standard dose RT

Interventions

Bevacizumab Injection

Additional concurrent low-dose Bevacizumab with standard EBRT

Intervention Type: DRUG

Ultra-low-dose RT

Ultra-low-dose EBRT instead of standard dose RT

Intervention Type: RADIATION

Other Intervention Names

Concurrent low-dose Bevacizumab

Eligibility Criteria

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.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tata Memorial Centre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rahul Krishnatry, Dr

Role: PRINCIPAL_INVESTIGATOR

Tata Memorial Hospital

Locations

Tata Memorial Hospital

Mumbai, Maharashtra, India

Site Status: RECRUITING

Countries

India

Central Contacts

Rahul Krishnatry, Dr

Role: CONTACT

krishnatry@gmail.com

022-24177000 ext. 7028

Facility Contacts

Dr Rahul Krishnatry, MD

Role: primary

krishnatry@gmail.com

022-24177000 ext. 6023

Other Identifiers

3201

Identifier Type: -

Identifier Source: org_study_id