Low dose Bevacizumab with radiotherapy for DIPG patients

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

This study is testing if adding a low dose of Bevacizumab to regular radiotherapy can help newly diagnosed children with DIPG live longer and feel better based on how their tumors are behaving.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 3 Years to 18 Years
• Sex: All
• Sponsor: Tata Memorial Centre (Academic / other)
• Drugs / interventions: Bevacizumab, chemotherapy, radiation
• Locations: 1 site (Mumbai, Maharashtra)
• Trial ID: NCT04250064 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of low dose Bevacizumab combined with conventional radiotherapy on survival outcomes in newly diagnosed patients with Diffuse Intrinsic Pontine Glioma (DIPG). Patients will undergo MRI perfusion studies to classify their tumors as hyperperfused or hypoperfused. Hyperperfused patients will receive weekly low dose Bevacizumab alongside standard radiotherapy, while hypoperfused patients will receive ultra-low-dose radiotherapy. The goal is to improve treatment efficacy and patient outcomes based on tumor perfusion characteristics.

Who should consider this trial

Good fit: Ideal candidates are children aged 3 to 18 years with newly diagnosed, non-disseminated, treatment-naïve DIPG.

Not a fit: Patients with disseminated DIPG or those who have received prior treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates and quality of life for children diagnosed with DIPG.

How similar studies have performed: While the approach of using Bevacizumab in this context is novel, previous studies have shown potential benefits of similar strategies in other tumor types.

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.

Where this trial is running

Mumbai, Maharashtra

• Tata Memorial Hospital — Mumbai, Maharashtra, India (Recruiting)

Study contacts

• Principal investigator: Rahul Krishnatry, Dr — Tata Memorial Hospital
• Study coordinator: Rahul Krishnatry, Dr

Conditions DIPG