~183 spots leftby Apr 2027

SIACI Bevacizumab + Temozolomide and Radiation for Glioblastoma

Palo Alto (17 mi)
Overseen byJohn Boockvar, MD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Northwell Health
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy

Trial Summary

What is the purpose of this trial?This trial tests a new treatment for aggressive brain cancer by using Mannitol to open the brain's barrier and then delivering Bevacizumab directly into the brain's arteries. It aims to improve survival rates for patients with newly diagnosed Glioblastoma Multiforme. Bevacizumab, typically administered intravenously, has shown superior outcomes when delivered directly into the brain's arteries in patients with recurrent Glioblastoma Multiforme.
Is the combination of the drug Bevacizumab with radiation therapy and the drug Temozolomide a promising treatment for glioblastoma?Yes, the combination of Bevacizumab, radiation therapy, and Temozolomide is considered promising for treating glioblastoma. Bevacizumab helps make the blood vessels less leaky, allowing for more effective radiation therapy. Temozolomide is known to kill cancer cells by causing mutations and cell death. Together, these treatments aim to improve control over the tumor.2451011
What data supports the idea that SIACI Bevacizumab + Temozolomide and Radiation for Glioblastoma is an effective treatment?The available research shows that adding Bevacizumab to the standard treatment of Temozolomide and radiation for glioblastoma can help delay the progression of the disease, although it does not necessarily extend overall survival for all patients. Some studies suggest that certain groups of patients might benefit more in terms of survival. However, there are safety concerns, as Bevacizumab has been linked to serious side effects like stroke and bleeding. Overall, while there are some benefits, the treatment's effectiveness varies, and it comes with potential risks.25679
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, if you have already started chemotherapy or radiation for GBM, you cannot participate in this trial.
What safety data is available for the treatment of glioblastoma with Bevacizumab, Temozolomide, and Radiation?Safety data for the combination of Bevacizumab, Temozolomide, and Radiation in treating glioblastoma includes findings from several studies. A Phase III trial highlighted concerns about stroke, bleeding, and wound-healing complications associated with Bevacizumab, especially in highly vascular tumors like glioblastoma. A Phase II study focused on the efficacy and toxicity of this combination. Another report discussed the risk of arterial and venous thromboembolism and hemorrhage with Bevacizumab, noting a case of dural venous sinus thrombosis. An interim analysis of a Phase II pilot study assessed safety and tolerability in newly diagnosed patients. Additionally, research on immune modulation by VEGF blockade in glioblastoma patients provided insights into systemic and tumor microenvironment changes.12378

Eligibility Criteria

This trial is for adults over 18 with newly diagnosed GBM brain cancer, expected to live at least 6 months. They must be able to have an MRI, use birth control if of reproductive potential, and sign consent. Participants need normal blood counts and organ function, a specific diagnosis of GBM per WHO criteria, and a Karnofsky Performance Status of 70% or higher.

Inclusion Criteria

I am not pregnant and agree to use birth control.
I am mostly able to care for myself and carry out daily activities.
My brain tumor is confirmed as GBM, IDH-wild type, according to 2021 WHO standards.

Exclusion Criteria

I am currently pregnant or breastfeeding.
I have started treatment for glioblastoma.
My scans show cancer has spread to multiple areas or the lining of my brain/spine.
I am currently being treated for an infection.
I don't have any health conditions that could risk my safety or affect the study.
My brain tumor is not a glioblastoma but has an IDH mutation.

Treatment Details

The study compares two treatments for GBM: one group receives standard Temozolomide with Radiation; the other gets an additional treatment called SIACI Bevacizumab (Avastin) alongside Temozolomide and Radiation. The goal is to see if SIACI increases survival without disease progression or overall lifespan compared to the standard therapy.
2Treatment groups
Experimental Treatment
Active Control
Group I: SIACI of Bevacizumab (Avastin) with Temozolomide and RadiationExperimental Treatment1 Intervention
Repeated Superselective Intraarterial Cerebral infusion (SIACI) of Bevacizumab (Avastin) with Temozolomide and Radiation
Group II: Standard of care Temozolomide and RadiationActive Control1 Intervention
Standard of care Temozolomide and Radiation
Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:
πŸ‡ͺπŸ‡Ί Approved in European Union as Avastin for:
  • Colorectal cancer
  • Breast cancer
  • Non-small cell lung cancer
  • Renal cell carcinoma
  • Ovarian cancer
πŸ‡ΊπŸ‡Έ Approved in United States as Avastin for:
  • Colorectal cancer
  • Non-small cell lung cancer
  • Glioblastoma
  • Renal cell carcinoma
  • Cervical cancer
  • Ovarian cancer
πŸ‡―πŸ‡΅ Approved in Japan as Avastin for:
  • Colorectal cancer
  • Non-small cell lung cancer
  • Breast cancer
  • Renal cell carcinoma
  • Ovarian cancer
πŸ‡¨πŸ‡¦ Approved in Canada as Avastin for:
  • Colorectal cancer
  • Non-small cell lung cancer
  • Breast cancer
  • Renal cell carcinoma
  • Ovarian cancer

Find a clinic near you

Research locations nearbySelect from list below to view details:
Lenox Hill Brain Tumor CenterNew York, NY
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Who is running the clinical trial?

Northwell HealthLead Sponsor

References

Phase II pilot study of bevacizumab in combination with temozolomide and regional radiation therapy for up-front treatment of patients with newly diagnosed glioblastoma multiforme: interim analysis of safety and tolerability. [2022]To assess interim safety and tolerability of a 10-patient, Phase II pilot study using bevacizumab (BV) in combination with temozolomide (TMZ) and regional radiation therapy (RT) in the up-front treatment of patients with newly diagnosed glioblastoma.
Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. [2022]This open-label, prospective, multicenter single-arm phase II study combined bevacizumab (BV) with radiation therapy (RT) and temozolomide (TMZ) for the treatment of newly diagnosed glioblastoma (GBM). The objectives were to determine the efficacy of this treatment combination and the associated toxicity.
Dural venous sinus thrombosis in anaplastic astrocytoma following concurrent temozolomide and focal brain radiotherapy plus bevacizumab. [2021]Malignant gliomas have long been a therapeutic dilemma in neuro-oncology, with a poor overall prognosis. Standard treatment, consisting of primary resection, followed by radiation therapy and temozolomide, has improved prognosis. Recently, studies have looked at the addition of bevacizumab (Avastin), a humanized murine IgG1 monoclonal antibody against vascular endothelial growth factor-A, to conventional regiments. Bevacizumab gained US FDA approval for single agent use in recurrent glioblastoma in 2009. Known side effects of bevacizumab include increased risk of arterial and venous thromboembolism, as well as hemorrhage. With emerging data for the use of bevacizumab in malignant gliomas, the extent of risks such as bleeding and thrombosis in patients with primary brain tumors treated with bevacizumab remains unknown. Here, we present only the second reported case of dural venous sinus thrombosis during treatment with bevacizumab and the first reported case for a primary glioma treated with temozolomide, radiation, and bevacizumab.
Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. [2022]Standard therapy for newly diagnosed glioblastoma is radiotherapy plus temozolomide. In this phase 3 study, we evaluated the effect of the addition of bevacizumab to radiotherapy-temozolomide for the treatment of newly diagnosed glioblastoma.
Phase II study of bevacizumab, temozolomide, and hypofractionated stereotactic radiotherapy for newly diagnosed glioblastoma. [2022]Bevacizumab is associated with decreased vascular permeability that allows for more aggressive radiotherapy schedules. We conducted a phase II trial in newly diagnosed glioblastoma utilizing a novel hypofractionated stereotactic radiotherapy (HFSRT) schedule combined with temozolomide and bevacizumab.
Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial. [2022]The AVAglio (Avastin in Glioblastoma) and RTOG-0825 randomized, placebo-controlled phase III trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy plus temozolomide. To establish whether certain patient subgroups derived an OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular subtype, and bevacizumab efficacy was assessed for each patient subgroup.
Bevacizumab, temozolomide, and radiotherapy for newly diagnosed glioblastoma: comprehensive safety results during and after first-line therapy. [2022]The proposed use of bevacizumab with radiotherapy/temozolomide for newly diagnosed glioblastoma raised potential safety concerns. Bevacizumab has been linked with stroke, bleeding events, and wound-healing complications in other tumor types; these events are of particular concern for glioblastoma (highly vascular tumors that are usually resected). Published data on the interaction of bevacizumab with radiotherapy/temozolomide are also limited. We report safety data from a phase III randomized trial (Avastin in Glioblastoma), focusing on these considerations.
Immune modulation associated with vascular endothelial growth factor (VEGF) blockade in patients with glioblastoma. [2018]Vascular endothelial growth factor (VEGF), in addition to being pro-angiogenic, is an immunomodulatory cytokine systemically and in the tumor microenvironment. We previously reported the immunomodulatory effects of radiation and temozolomide (TMZ) in newly diagnosed glioblastoma. This study aimed to assess changes in peripheral blood mononuclear cell (PBMC) populations, plasma cytokines, and growth factor concentrations following treatment with radiation, TMZ, and bevacizumab (BEV).
Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial. [2018]A pilot study of temozolomide (TMZ) given before radiotherapy (RT) for anaplastic astrocytoma (AA) and glioblastoma (GBM) resulted in prolonged survival compared to historical controls receiving RT alone. We therefore investigated neoadjuvant TMZ (NeoTMZ) in a randomized trial. During enrollment, concomitant and adjuvant radio-chemotherapy with TMZ became standard treatment. The trial was amended to include concurrent TMZ.
Bevacizumab plus hypofractionated radiotherapy versus radiotherapy alone in elderly patients with glioblastoma: the randomized, open-label, phase II ARTE trial. [2020]The addition of bevacizumab to temozolomide-based chemoradiotherapy (TMZ/RT β†’ TMZ) did not prolong overall survival (OS) in patients with newly diagnosed glioblastoma in phase III trials. Elderly and frail patients are underrepresented in clinical trials, but early reports suggested preferential benefit in this population.
Radiosensitization of Glioma Cells by Temozolomide (TMZ): A Colony Formation Assay. [2022]Glioblastoma is one of the most radioresistant cancers. It is suggested that combination of radiotherapy with other cancer treatment modalities may increase control of tumor. Temozolomide (TMZ) is one of the most known drugs for glioblastoma. It has shown that TMZ via induction of mutation and cell death can kill glioma cells.