Trial Summary
What is the purpose of this trial?The goal of this interventional study is to evaluate the efficacy of APG-157 in combination with Bevacizumab in subjects with recurrent high-grade glioma. The main questions the study aims to answer are:
* Progression-free and overall survival of patients receiving this combination;
* Quality of Life (QOL); and
* Tumor response on imaging
The participants will take APG-157 daily by dissolving two pastilles in their mouth at around breakfast, lunch and dinner time (total of six pastilles per day). The pastilles dissolve in the mouth.
The participants will continue to receive Bevacizumab as standard of care.
What safety data exists for APG-157 and Bevacizumab in brain tumor treatment?The provided research primarily discusses the safety of Bevacizumab in various contexts, including high-grade glioma and brain metastases. Bevacizumab has been evaluated for its safety profile, with studies noting its use in recurrent malignant glioma and brain metastases from non-small cell lung cancer. Adverse events such as CNS hemorrhage have been a concern, but studies have shown a low incidence of such events. However, there is no specific safety data available for APG-157 in the provided research.23457
What data supports the idea that APG-157 + Bevacizumab for Brain Tumor is an effective treatment?The available research shows that Bevacizumab, when used alone, can delay the progression of brain tumors, but it has limited benefits on overall survival. In a study with 160 patients, the median time before the disease got worse was 4 months, and about 29% of patients did not see their disease progress for 6 months. However, the overall survival rate was not significantly improved, with only 28% of patients surviving 9 months. This suggests that while Bevacizumab can help slow down the disease, it may not significantly extend life expectancy. There is no specific data on APG-157 combined with Bevacizumab, so its effectiveness compared to other treatments is unclear.146910
Is the drug APG-157 a promising treatment for brain tumors?The information provided does not directly address the effectiveness of APG-157 for brain tumors. However, the combination of APG-157 with bevacizumab, which has shown potential in treating certain brain conditions, suggests that APG-157 might be promising. Further research would be needed to confirm its effectiveness.347810
Do I have to stop taking my current medications for this trial?The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had immunotherapy, chemotherapy, radiotherapy, or experimental therapy within one full cycle period before the first dose of the study drug. It's best to discuss your current medications with the trial team.
Eligibility Criteria
This trial is for adults (19+) with high-grade glioma brain tumors that have worsened despite previous treatments including Bevacizumab, radiation, and temozolomide. Participants must be in stable health otherwise, with good organ function and blood counts. Pregnant or nursing women can't join, nor those with recent heart issues or surgeries.Inclusion Criteria
My high-grade brain tumor has worsened despite bevacizumab treatment.
I am 19 years old or older.
My blood tests show enough white cells, hemoglobin, and platelets.
My kidney function is within the normal range based on creatinine levels.
I am not pregnant or nursing and agree to use birth control during and 6 months after the study.
I can care for myself but may not be able to do heavy physical work.
Exclusion Criteria
My blood pressure is not controlled by medication and is higher than 160/90 mm Hg.
I have not had major surgery or a significant injury in the last 28 days.
I have an active or non-healing wound, ulcer, or untreated bone fracture.
Treatment Details
The study tests APG-157 pastilles taken orally three times daily alongside standard Bevacizumab treatment. It aims to assess the combination's impact on tumor progression, patient survival rates, quality of life, and changes observed in imaging studies.
1Treatment groups
Experimental Treatment
Group I: APG-157Experimental Treatment1 Intervention
The participants will receive APG-157 daily by taking two pastilles in their mouth at around breakfast, lunch and dinner time (total of six pastilles per day). The pastilles dissolve in the mouth.
The participants will continue to receive Bevacizumab as standard of care.
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of Nebraska Medical CenterOmaha, NE
Mayo ClinicRochester, MN
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Who is running the clinical trial?
Aveta Biomics, Inc.Lead Sponsor
References
Role of a second chemotherapy in recurrent malignant glioma patients who progress on bevacizumab. [2022]Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor (VEGF) that has efficacy in recurrent malignant gliomas, particularly in combination with irinotecan. However, responses are rarely durable. Continuation of bevacizumab in combination with another chemotherapeutic agent may demonstrate some activity. In this article we present a retrospective review of 54 patients with recurrent malignant gliomas who progressed on a bevacizumab-containing regimen and were then treated with an alternate bevacizumab-containing regimen. All patients received intravenous bevacizumab (5-10 mg/kg) every 2 weeks alone or in combination with an additional chemotherapeutic agent, such as irinotecan. There was no limit on the number of prior therapies. Clinical characteristics and outcomes were reviewed. Tumor progression was determined by a combination of clinical status and radiographic changes. Patients were 33 men, 21 women (median age, 50 years; range, 23-72 years) with a median KPS score of 80 prior to the first bevacizumab-containing regimen and 70 prior to the second regimen; median prior chemotherapy regimens including the first bevacizumab-containing regimen was 3 (range, 2-5). Median progression-free survival (PFS) on the first bevacizumab-containing regimen was 124 days (95% confidence interval [CI], 87-154 days); 6-month (6M)-PFS was 33%. Median PFS on the second bevacizumab-containing regimen was 37.5 days (95% CI, 34-42 days); 6M-PFS was 2%. Ten patients on the first regimen and 12 patients on the second regimen suffered grade 3/4 toxicities. Those patients with malignant gliomas who progressed despite a bevacizumab-containing regimen rarely responded to the second bevacizumab-containing chemotherapeutic regimen. In such patients, alternate therapies should be considered.
Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases. [2022]Patients with non-small-cell lung cancer (NSCLC) and brain metastases have previously been excluded from trials of bevacizumab because of suspected risk of CNS hemorrhage. This phase II trial, AVF3752g (PASSPORT), specifically addressed bevacizumab safety (incidence of grade > or = 2 CNS hemorrhage) in patients with NSCLC and previously treated brain metastases.
Efficacy and safety of bevacizumab in active brain metastases from non-small cell lung cancer. [2022]Bevacizumab is effective for the treatment of non-small cell lung cancer (NSCLC). Ongoing trials are exploring the safety of bevacizumab in patients with inactive, previously treated brain metastases. However, bevacizumab safety and efficacy in the treatment of active brain metastases is unknown. Bevacizumab received accelerated FDA approval for progressive glioblastoma, a primary brain tumor, because of high response rates and low incidence of intracranial hemorrhage. We retrospectively identified patients treated with bevacizumab for active (treatment naïve or progressive) central nervous system (CNS) metastases from NSCLC. MRI scans performed at least 6 weeks after initiating bevacizumab were assessed for response. There were six patients, four women and two men with a median age of 60 years (range 59-77) at initiation of bevacizumab. Five patients had progressive CNS metastases despite prior treatment including surgery, radiotherapy, and/or chemotherapy; one patient had treatment-naïve brain metastases. Two patients had leptomeningeal metastases, isolated or coexistent with parenchymal brain metastases in one patient each. Bevacizumab was administered alone to one patient and in combination with various cytotoxic chemotherapies in the others. Toxicity included an asymptomatic (Grade 1) intra-tumoral hemorrhage which occurred in one of three patients receiving concurrent anticoagulation with bevacizumab. There was no recurrent CNS bleeding in two patients with a prior history of such hemorrhage. Best CNS response (RECIST) was partial in two, stable disease in three, and progression in one. Median progression-free survival (PFS) was 7.8 months and median overall survival (OS) was 14.1 months following initiation of bevacizumab. Clinical benefit was also observed in the form of improved symptoms and reduced corticosteroid requirements. Bevacizumab should be used with caution in patients with active CNS metastases pending additional safety data. This series suggests bevacizumab may be safe and effective for progressive brain metastases from NSCLC and deserves further study.
Lack of efficacy of bevacizumab plus irinotecan in children with recurrent malignant glioma and diffuse brainstem glioma: a Pediatric Brain Tumor Consortium study. [2022]A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent malignant glioma (MG) and intrinsic brainstem glioma (BSG).
Bevacizumab use for recurrent high-grade glioma at McGill University Hospital. [2019]Bevacizumab, a humanized recombinant anti-vascular endothelial growth factor antibody, was approved in Canada in 2010 for the treatment of high-grade glioma. We report the effectiveness and safety of bevacizumab in the treatment of patients with recurrent high-grade gliomas at a single institution.
Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas--a Pediatric Brain Tumor Consortium study. [2022]A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent low-grade glioma to measure sustained response and/or stable disease lasting ≥6 months and progression-free survival.
[Preliminary clinical evaluations of bevacizumab for recurrent malignant glioma in Chinese patients]. [2015]To explore the clinical efficacies of bevacizumab (BEV) for high-grade glioma (HGG) in Chinese patients and evaluate its profiles of adverse events and usage safety.
Genetic modification of neurons to express bevacizumab for local anti-angiogenesis treatment of glioblastoma. [2018]The median survival of glioblastoma multiforme (GBM) is approximately 1 year. Following surgical removal, systemic therapies are limited by the blood-brain barrier. To circumvent this, we developed a method to modify neurons with the genetic sequence for therapeutic monoclonal antibodies using adeno-associated virus (AAV) gene transfer vectors, directing persistent, local expression in the tumor milieu. The human U87MG GBM cell line or patient-derived early passage GBM cells were administered to the striatum of NOD/SCID immunodeficient mice. AAVrh.10BevMab, an AAVrh.10-based vector coding for bevacizumab (Avastin), an anti-human vascular endothelial growth factor (VEGF) monoclonal antibody, was delivered to the area of the GBM xenograft. Localized expression of bevacizumab was demonstrated by quantitative PCR, ELISA and western blotting. Immunohistochemistry showed that bevacizumab was expressed in neurons. Concurrent administration of AAVrh.10BevMab with the U87MG tumor reduced tumor blood vessel density and tumor volume, and increased survival. Administration of AAVrh.10BevMab 1 week after U87MG xenograft reduced growth and increased survival. Studies with patient-derived early passage GBM primary cells showed a reduction in primary tumor burden with an increased survival. These data support the strategy of AAV-mediated central nervous system gene therapy to treat GBM, overcoming the blood-brain barrier through local, persistent delivery of an anti-angiogenesis monoclonal antibody.
Clinical effectiveness of bevacizumab in patients with recurrent brain tumours: A population-based evaluation. [2022]Background Bevacizumab is an antiangiogenic agent active in patients with recurrent malignant gliomas. However, evidence for its clinical efficacy is relatively limited so that bevacizumab is approved for this indication in Canada and the United States, but not in the European Union. We reviewed the effectiveness of bevacizumab in patients with recurrent brain tumour using a large population database. Methods This was a retrospective, multicentre, study conducted at the BC Cancer Agency, a public cancer care organisation for the residents of the Canadian province of British Columbia. Cases were identified from the provincial registry and drug database. Patients were eligible if they were treated with bevacizumab with or without lomustine or etoposide for recurrent brain tumour between April 2011 and March 2014. The primary end points were progression-free survival. Secondary endpoints were overall survival and objective response rate. Results A total of 160 patients were included, with a median age of 55 years. The most common diagnosis was glioblastoma multiforme (70.6%), followed by oligodendroglioma (10.6%). Half of the patients had prior metronomic dosing of temozolomide. The median duration of therapy was 3 months. The median progression-free survival was 4.0 months and the 6-month progression-free survival was 29.4%. The median overall survival was 7 months and the 9-month and 12-month overall survival was 28.1% and 20.6%, respectively. The objective response rate was 23.1%. The most common documented reason for bevacizumab discontinuation was disease progression (66.9%), followed by toxicity (6.9%). Conclusions Bevacizumab therapy seems to be effective in delaying disease progression in patients with recurrent brain tumour, but with limited benefits on the overall survival, when used outside the clinical trial setting.
Therapeutic effect and side effects of Bevacizumab combined with Irinotecan in the treatment of paediatric intracranial tumours: Meta-analysis and Systematic Review. [2021]Bevacizumab (BVZ) is an angiogenesis inhibitor that often works well with chemotherapeutic drugs for the treatment of solid intracranial tumours in children. This meta-analysis discusses the efficacy and side effects of BVZ combined with irinotecan in the treatment of patients (younger than 21 years of age) with recurrent, progressive or refractory intracranial tumours.