Vinblastine + Bevacizumab for Brain Tumor

Not currently recruiting at 23 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding Bevacizumab (Avastin) to Vinblastine improves treatment for children with progressive Low Grade Glioma, a type of brain tumor. Participants will receive either Vinblastine alone or Vinblastine with Bevacizumab. The trial seeks children or teens who haven't undergone chemotherapy and have a growing or incompletely removed brain tumor. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of Vinblastine and Bevacizumab is being tested for safety in children with brain tumors. Previous studies found that Bevacizumab, when combined with other chemotherapy drugs, can improve survival rates without causing severe side effects compared to using Bevacizumab alone. This suggests that the combination might be well-tolerated.

Vinblastine is a chemotherapy drug used for other types of cancer, and its side effects are well-known. Common side effects include low blood cell counts, which can increase infection risk, and hair loss.

While this trial will provide more specific safety information for the combination in low-grade glioma, existing research offers a hopeful sign regarding its tolerability. Always discuss potential risks with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of vinblastine and bevacizumab for brain tumors because it offers a novel approach compared to current treatments. Unlike standard chemotherapy options, this combination targets the tumor's blood supply with bevacizumab, an anti-angiogenic agent, potentially starving the tumor of nutrients and slowing its growth. Additionally, vinblastine is a well-known chemotherapy agent, but its combination with bevacizumab could enhance its effectiveness by disrupting multiple pathways crucial for tumor survival. This dual-action approach aims to improve outcomes for patients with brain tumors beyond what current therapies can offer.

What evidence suggests that this trial's treatments could be effective for brain tumors?

Research has shown that Bevacizumab, when combined with other treatments, can help patients with brain tumors live longer without disease progression. One study found that combining Bevacizumab with chemotherapy increased the number of patients whose tumors shrank or stopped growing. In this trial, participants in Arm B will receive a combination of Vinblastine and Bevacizumab to determine if this combination improves results for children with brain tumors. Participants in Arm A will receive Vinblastine alone, which has proven effective in treating low-grade gliomas, a type of brain tumor. Researchers aim to discover if adding Bevacizumab can enhance outcomes for these patients. ^{1 4 5 6 7}

Who Is on the Research Team?

Eric Bouffet, MD

Principal Investigator

The Hospital for Sick Children

Are You a Good Fit for This Trial?

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

Patients with evidence of new symptomatic CNS hemorrhage on baseline MRI

My child is under 6 months old.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12311935/

Bevacizumab alternating chemotherapy for improving the ... This study evaluated a bevacizumab alternating chemotherapy (BAC) regimen, which alternated between 2 combinations, etoposide (ETP) + carboplatin (CB) and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02840409

NCT02840409 | Vinblastine +/- Bevacizumab in Children ... To evaluate the difference in visual outcome measures in children with optic pathway gliomas treated with vinblastine alone or in combination with Bevacizumab.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1878875024017753

Efficacy and Safety of Bevacizumab Combined with ... The combination of TMZ and BEV can improve PFS as well as overall response rate in patients and has no benefit on OS.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7034747/

A long-term retrospective study in Taiwan - PubMed Central This study revealed combination regimen of bevacizumab, vincristine, and low-dose carboplatin as a potentially effective therapeutic approach in recurrent ...

5. targetedonc.com targetedonc.com/view/unveiling-the-potential-of-combined-therapies-for-glioblastoma

Unveiling the Potential of Combined Therapies for ... Previous studies have shown limited success with immunotherapy alone for this aggressive brain cancer. The trial compared a standard dose and a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12564347/

Bevacizumab in Pediatric Neuro-Oncology - PMC Despite advancements in treatment, the 5-year survival rate remains dismal, below 20% [23,24]. The standard of care for pHGG involves maximal ...

7. academic.oup.com academic.oup.com/noa/advance-article/doi/10.1093/noajnl/vdaf157/8209513

Bevacizumab alternating chemotherapy for improving the ... Their study found that patients who received bevacizumab with chemotherapy lived longer than those who received bevacizumab alone. This benefit ...