SIACI Bevacizumab + Temozolomide and Radiation for Glioblastoma
Recruiting in 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
Disqualifiers: Other malignancy, Active infection, HIV, others
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.
Do I need to stop my current medications to join the trial?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the treatment Bevacizumab, Temozolomide, and Radiation Therapy for glioblastoma?
Research shows that adding bevacizumab to radiotherapy and temozolomide can prolong the time before glioblastoma worsens, although it may not extend overall survival for all patients. Some studies suggest certain subgroups might benefit more from this combination.
12345Is the combination of Bevacizumab, Temozolomide, and Radiation Therapy safe for humans?
The combination of Bevacizumab, Temozolomide, and Radiation Therapy for glioblastoma has shown some safety concerns, including risks of stroke, bleeding, and blood clots. Bevacizumab, in particular, is associated with these risks, and its interaction with the other treatments is still being studied.
23678What makes the SIACI Bevacizumab + Temozolomide and Radiation treatment unique for glioblastoma?
This treatment combines bevacizumab, which reduces blood vessel leakage, with temozolomide, a drug that kills cancer cells by causing mutations, and a specialized form of radiation therapy. This combination aims to enhance the effectiveness of radiation by making the tumor more sensitive to it, potentially offering better control of the tumor compared to standard treatments.
3491011Eligibility 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.
Subject must be able to undergo MRI evaluation
+6 more
Exclusion Criteria
I am currently pregnant or breastfeeding.
Subject has a known positive test for human immunodeficiency virus infection, or active hepatitis B or hepatitis C infection
I have started treatment for glioblastoma.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Subjects receive Mannitol followed by repeated IA BV infusion and chemoradiation. IA BV is repeated every three months for a total of 3 infusions.
9 months
3 visits (in-person) for IA BV infusions
Follow-up
Participants are monitored for overall survival and progression-free survival, with assessments for adverse events and quality of life.
62 months
Participant Groups
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:
πͺπΊ Approved in European Union as Avastin for:
- Colorectal cancer
- Breast cancer
- Non-small cell lung cancer
- Renal cell carcinoma
- Ovarian cancer
πΊπΈ Approved in United States as Avastin for:
- Colorectal cancer
- Non-small cell lung cancer
- Glioblastoma
- Renal cell carcinoma
- Cervical cancer
- Ovarian cancer
π―π΅ Approved in Japan as Avastin for:
- Colorectal cancer
- Non-small cell lung cancer
- Breast cancer
- Renal cell carcinoma
- Ovarian cancer
π¨π¦ 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
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.