Vinblastine + Bevacizumab for Brain Tumor

Recruiting at 20 trial locations

Overseen By Emily Taylor

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: The Hospital for Sick Children

Must not be taking: Aspirin, Clopidogrel, Anticoagulants

Disqualifiers: Pregnancy, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 68 weeks

109 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like high-dose aspirin, clopidogrel, and some anticoagulants must be stopped or adjusted before enrollment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Vinblastine and Bevacizumab for brain tumors?

Bevacizumab has shown effectiveness in reducing tumor growth in high-grade gliomas and brain metastases by targeting VEGF, a protein that promotes blood vessel growth in tumors. Vinblastine has demonstrated activity in shrinking low-grade gliomas in children, suggesting potential benefits when combined with Bevacizumab for brain tumors. ^{1 2 3 4 5}

Is the combination of Vinblastine and Bevacizumab safe for treating brain tumors?

Bevacizumab, one of the drugs in this treatment, has been linked to an increased risk of serious side effects like strokes and bleeding in the brain, especially at higher doses and in certain cancer types. It's important to discuss these risks with your doctor to understand how they might apply to your situation. ^{2 6 7 8 9}

How is the drug combination of Vinblastine and Bevacizumab unique for treating brain tumors?

The combination of Vinblastine and Bevacizumab is unique because Vinblastine has shown effectiveness in shrinking tumors by reducing their blood supply, while Bevacizumab targets and blocks a protein that helps tumors form new blood vessels, potentially slowing tumor growth and reducing swelling in the brain. ^{1 4 10 11 12}

What is the purpose of this trial?

This trial is testing if adding Bevacizumab to Vinblastine helps children with worsening brain tumors more than using Vinblastine alone. Vinblastine is given regularly, and Bevacizumab is added periodically for several months. Bevacizumab is an anti-VEGF antibody approved for treating various cancers and has been studied for use in children with brain tumors.

Research Team

Eric Bouffet, MD

Principal Investigator

The Hospital for Sick Children

Eligibility Criteria

This trial is for children and teens aged 6 months to less than 18 years with Low Grade Glioma (brain tumor) who haven't had previous treatments except surgery. They must be able to start treatment within two weeks after joining, have stable health conditions, and meet specific blood, liver, kidney function criteria. Sexually active teens must use contraception.

Inclusion Criteria

My liver functions properly.

I am between 6 months and 18 years old with a Low Grade Glioma.

My cancer has worsened after surgery.

Exclusion Criteria

Hypersensitivity to Chinese hamster ovary (CHO) cell products or other recombinant human or humanized antibodies

My child is under 6 months old.

I have not used any experimental drugs before starting this study treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Vinblastine weekly for 68 weeks. Arm B includes additional Bevacizumab every two weeks for the first 24 weeks.

68 weeks

Weekly visits for Vinblastine, bi-weekly for Bevacizumab in Arm B

Follow-up

Participants are monitored for safety, effectiveness, and long-term outcomes after treatment completion.

5 years

Annual visits

Long-term follow-up

Evaluation of cognitive, fertility, and quality of life outcomes, including annual assessments.

5 years

Treatment Details

Interventions

• Bevacizumab
• Vinblastine

Trial Overview The study tests if adding Bevacizumab to Vinblastine improves outcomes in pediatric patients with progressive brain tumors. It's a Phase II trial where participants are randomly assigned to receive either just Vinblastine or both drugs over a period of 68 weeks.

Participant Groups

Group I: Arm B Experimental Treatment 2 Interventions

68 weeks of Vinblastine administered weekly IV with the addition of 12 doses of Bevacizumab administered every two weeks IV for the initial 24 weeks.

Group II: Arm A Active Control 1 Intervention

68 weeks of single agent Vinblastine administered once weekly IV

Vinblastine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Velban for:

• Hodgkin lymphoma
• Non-Hodgkin lymphoma
• Testicular cancer
• Choriocarcinoma
• Kaposi's sarcoma

Approved in European Union as Vinblastine sulfate for:

• Hodgkin lymphoma
• Non-Hodgkin lymphoma
• Testicular cancer
• Choriocarcinoma

Approved in Canada as Vinblastine sulfate for:

• Hodgkin lymphoma
• Non-Hodgkin lymphoma
• Testicular cancer
• Choriocarcinoma

Who Is Running the Clinical Trial?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

Hoffmann-La Roche

Industry Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

In a phase II study involving 51 pediatric patients with recurrent low-grade glioma, vinblastine treatment resulted in a 36% response rate, indicating its potential efficacy as an alternative to radiation for patients who have failed previous treatments.

The study reported a 5-year overall survival rate of 93.2% and a 5-year progression-free survival rate of 42.3%, suggesting that vinblastine is a viable option for managing low-grade gliomas in children, with manageable toxicity primarily affecting blood cell counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of weekly vinblastine in recurrent or refractory pediatric low-grade glioma. Bouffet, E., Jakacki, R., Goldman, S., et al.[2022]

Bevacizumab significantly increases the risk of cerebrovascular events, including CNS ischemic events and CNS hemorrhage, with a relative risk of 3.28 based on a meta-analysis of 17 randomized controlled trials involving 12,917 patients.

The risk of cerebrovascular events varies with the dose of bevacizumab and is particularly high in patients with metastatic colorectal cancer, indicating that careful monitoring is needed for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased risk of cerebrovascular events in patients with cancer treated with bevacizumab: a meta-analysis. Zuo, PY., Chen, XL., Liu, YW., et al.[2021]

Inhibiting vascular endothelial growth factor (VEGF) with agents like bevacizumab is intended to normalize tumor blood vessels, potentially improving drug delivery and radiotherapy effectiveness for primary CNS tumors.

However, concerns have emerged that these agents may restore the blood-brain barrier's low permeability too quickly, which could reduce the effectiveness of standard treatments like radiochemotherapy and increase tumor infiltration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The paradoxical effect of bevacizumab in the therapy of malignant gliomas. Thompson, EM., Frenkel, EP., Neuwelt, EA.[2021]

A study of 310 glioblastoma patients from 2010 to 2014 found that the use of bevacizumab did not improve overall survival compared to patients treated before its approval, with median survival remaining similar at 13.5 months for IDH wild-type tumors.

However, patients receiving bevacizumab experienced a significant reduction in corticosteroid use during second-line treatment, suggesting a potential clinical benefit in managing treatment side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab may improve quality of life, but not overall survival in glioblastoma: an epidemiological study. Gramatzki, D., Roth, P., Rushing, EJ., et al.[2020]

Bevacizumab, a monoclonal antibody that targets VEGF, has been shown to reduce tumor growth and associated brain swelling in glioblastoma patients, potentially improving their quality of life and survival rates.

Despite its benefits, the review highlights the importance of understanding the potential side effects and complications of bevacizumab, as well as exploring new drug combinations to enhance its efficacy in treating glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of bevacizumab therapy in the management of glioblastoma. Peak, SJ., Levin, VA.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

The anti-VEGF antibody bevacizumab potently reduces the growth rate of high-risk neuroblastoma xenografts. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Bevacizumab in high-grade gliomas: past, present, and future. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Phase II study of weekly vinblastine in recurrent or refractory pediatric low-grade glioma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

The use of neo adjuvant single-agent vinblastine for tumour shrinkage in a highly vascular paediatric low-grade glioma. [2020]

5. China pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bevacizumab combined with chemotherapy in symptomatic brain metastases from lung adenocarcinoma: a retrospective analysis. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Increased risk of cerebrovascular events in patients with cancer treated with bevacizumab: a meta-analysis. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

The paradoxical effect of bevacizumab in the therapy of malignant gliomas. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Intra-arterial delivery of bevacizumab after blood-brain barrier disruption for the treatment of recurrent glioblastoma: progression-free survival and overall survival. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Bevacizumab may improve quality of life, but not overall survival in glioblastoma: an epidemiological study. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Notable response of a young adult with recurrent glioblastoma multiforme to vincristine-irinotecan-temozolomide and bevacizumab. [2023]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Role of bevacizumab therapy in the management of glioblastoma. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Combination of bevacizumab, irinotecan, and temozolomide for refractory or relapsed neuroblastoma: Results of a phase II study. [2023]