APG-157 + Bevacizumab for Brain Tumor

Recruiting at 1 trial location

Overseen By Nicole Shonka, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Aveta Biomics, Inc.

Must be taking: Bevacizumab

Must not be taking: Immunotherapy, Chemotherapy

Disqualifiers: Pregnancy, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 8

Duration: 12 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with high-grade glioma that has recurred after previous treatments. The researchers aim to determine if combining APG-157, a new oral treatment, with Bevacizumab, an existing treatment, can extend the time patients live without disease progression, enhance their quality of life, and reduce tumor size. Participants will take APG-157 by dissolving pastilles in their mouth throughout the day while continuing their usual Bevacizumab treatment. Suitable candidates have high-grade glioma that has progressed after previous treatments, including Bevacizumab, and have completed radiation and chemotherapy at least three months prior. As a Phase 1/Phase 2 trial, this study focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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.

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

Research has shown that APG-157 is generally safe for people. In studies where patients used APG-157, they tolerated it well, and serious side effects were rare. APG-157 has also been studied as a treatment for head and neck cancers, and the FDA has shown special interest in its potential benefits, which adds confidence in its safety.

Participants in this trial will also take Bevacizumab, a drug already approved by the FDA for other conditions, such as brain tumors. Its safety is well-known, though it may have side effects like any drug.

Overall, while no treatment is without risk, available data suggests that APG-157 combined with Bevacizumab has a promising safety record based on previous research and current medical use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain tumors?

Unlike the standard treatments for brain tumors, which often include surgery, radiation, and chemotherapy, APG-157 offers a unique approach by using a natural compound that dissolves in the mouth. This delivery method allows the active ingredients to be absorbed directly into the bloodstream, potentially increasing its effectiveness. Researchers are excited about APG-157 because it may target tumor cells with fewer side effects compared to traditional therapies, opening up new possibilities for more tolerable and efficient treatment options.

What evidence suggests that this treatment might be an effective treatment for recurrent high-grade glioma?

Research has shown that APG-157, when combined with Bevacizumab, may help treat high-grade glioma, a type of brain tumor. In this trial, participants will receive APG-157 alongside their standard care with Bevacizumab. Patients who previously used APG-157 experienced improvements in survival and quality of life. Bevacizumab is already known for slowing tumor growth by cutting off the tumor's blood supply. Researchers are testing APG-157 to see if it can enhance these effects. Early studies suggest that APG-157 might help people with recurring brain tumors live longer and feel better. However, more research is needed to confirm the effectiveness of this combination. ^{2 5 6 7 8}

Who Is on the Research Team?

Nicole Shonka, MD

Principal Investigator

University of Nebraska

Joon Uhm, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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

total bilirubin < 1.5 x ULN (unless due to Gilbert's disease)

I agree to participate in the trial and understand its risks and benefits.

I've had radiation and temozolomide treatment before.

Exclusion Criteria

I haven't had cancer treatments like immunotherapy or chemotherapy in the last 4-6 weeks.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive APG-157 daily and continue Bevacizumab as standard of care

12 months

Every 8 weeks for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• APG-157

Trial Overview

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.

How Is the Trial Designed?

Group I: APG-157 Experimental Treatment 1 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.

Who Is Running the Clinical Trial?

Aveta Biomics, Inc.

Lead Sponsor

Trials

4

Recruited

90+

Published Research Related to This Trial

In a study of 15 Chinese patients with high-grade glioma, bevacizumab (BEV) showed significant short-term clinical and radiological responses in 11 cases, but only 4 maintained responses beyond 3 months, indicating its effectiveness may be limited over time.

The treatment was generally well-tolerated, with manageable adverse events such as hypertension and vomiting, but it is recommended to delay BEV administration for one month after surgery to prevent wound-healing complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preliminary clinical evaluations of bevacizumab for recurrent malignant glioma in Chinese patients]. Lu, Y., Qi, S., Ouyang, H., et al.[2015]

In a phase II study involving 31 children with recurrent malignant glioma and brainstem glioma, the combination of bevacizumab (BVZ) and irinotecan (CPT-11) was well-tolerated but showed minimal efficacy, with no sustained responses observed.

The median time to progression was 127 days for malignant glioma and 71 days for brainstem glioma, indicating limited effectiveness of the treatment despite some patients experiencing temporary benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of efficacy of bevacizumab plus irinotecan in children with recurrent malignant glioma and diffuse brainstem glioma: a Pediatric Brain Tumor Consortium study. Gururangan, S., Chi, SN., Young Poussaint, T., et al.[2022]

In a phase II trial involving 115 patients with non-small-cell lung cancer (NSCLC) and treated brain metastases, the addition of bevacizumab to chemotherapy or erlotinib showed a low incidence of serious CNS hemorrhage, with no cases of grade 2 or higher reported among 106 safety-evaluable patients.

The study suggests that bevacizumab is safe for use in this patient population, as it was well-tolerated with a median treatment duration of 6.3 months and only a small percentage of patients (24.5%) discontinuing due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases. Socinski, MA., Langer, CJ., Huang, JE., et al.[2022]

In a small retrospective study of six patients with active brain metastases from non-small cell lung cancer (NSCLC), bevacizumab showed promising efficacy, with a median progression-free survival of 7.8 months and median overall survival of 14.1 months after treatment initiation.

While there was one case of asymptomatic intra-tumoral hemorrhage, no recurrent bleeding occurred in patients with a history of such events, suggesting that bevacizumab may be safe for use in this population, although caution is advised until more safety data is available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bevacizumab in active brain metastases from non-small cell lung cancer. De Braganca, KC., Janjigian, YY., Azzoli, CG., et al.[2022]

In a study of 27 patients with recurrent high-grade gliomas, bevacizumab demonstrated a clinical benefit rate of 59%, with a median progression-free survival (PFS) of 4.3 months and a six-month PFS rate of 43%.

The safety profile included some serious adverse events, with 10 episodes of grade 3/4 side effects, but overall, the efficacy and safety of bevacizumab were found to be comparable to other international studies on similar patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab use for recurrent high-grade glioma at McGill University Hospital. Sahebjam, S., Garoufalis, E., Guiot, MC., et al.[2019]

In a study of 160 patients with recurrent brain tumors, bevacizumab demonstrated a median progression-free survival of 4 months, indicating its effectiveness in delaying disease progression.

However, the overall survival benefit was limited, with a median overall survival of only 7 months, suggesting that while bevacizumab can help manage symptoms, it may not significantly extend life in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of bevacizumab in patients with recurrent brain tumours: A population-based evaluation. de Lemos, ML., Markarian, A., Chan, E., et al.[2022]

In a study of 54 patients with recurrent malignant gliomas, those who progressed on a first bevacizumab-containing regimen showed very limited response to a second bevacizumab-containing treatment, with a median progression-free survival of only 37.5 days.

The findings suggest that continuing bevacizumab after progression is not effective, and alternative therapies should be explored for these patients, as both regimens resulted in significant toxicities, with 10 patients experiencing grade 3/4 side effects on the first regimen and 12 on the second.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of a second chemotherapy in recurrent malignant glioma patients who progress on bevacizumab. Quant, EC., Norden, AD., Drappatz, J., et al.[2022]

In a phase II study involving 35 children with recurrent low-grade gliomas, the combination of bevacizumab (BVZ) and irinotecan (CPT-11) resulted in sustained disease control, with 83% of patients maintaining stable disease for at least 6 months.

The treatment showed a promising 6-month progression-free survival rate of 85.4% and a 2-year rate of 47.8%, although common side effects included hypertension, fatigue, and proteinuria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas--a Pediatric Brain Tumor Consortium study. Gururangan, S., Fangusaro, J., Poussaint, TY., et al.[2022]

In a meta-analysis of 13 studies involving 272 children with recurrent intracranial tumors, the combination of bevacizumab (BVZ) and irinotecan resulted in an objective response rate of 41%, with 28% achieving partial response and 13% achieving complete response, indicating its efficacy in treating these tumors.

The treatment led to a median progression-free survival of 6.47 months and overall survival of 11.9 months, while common side effects included gastrointestinal dysfunction, leukopenia, and hypertension, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic effect and side effects of Bevacizumab combined with Irinotecan in the treatment of paediatric intracranial tumours: Meta-analysis and Systematic Review. Xu, Y., Li, Q., Ma, HY., et al.[2021]

AAV-mediated gene therapy successfully delivered the anti-VEGF monoclonal antibody bevacizumab directly to glioblastoma tumors in mice, leading to reduced tumor volume and increased survival rates.

This method effectively circumvents the blood-brain barrier, demonstrating potential for localized and persistent treatment of glioblastoma multiforme, which typically has a median survival of only 1 year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic modification of neurons to express bevacizumab for local anti-angiogenesis treatment of glioblastoma. Hicks, MJ., Funato, K., Wang, L., et al.[2018]

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The purpose of this study is to assess the safety and effect of APG-157 on the six-month survival and quality of life (QoL) of patients with recurrent GBM.

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This expanded access administration will evaluate the potential of APG-157, a novel drug under development for head and neck cancer, as a potential treatment ...

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FDA Grants Fast Track Status to Neoadjuvant APG-157 in ...

Investigators are evaluating the efficacy and safety of APG-157 for patients with head and neck cancer in a phase 2 clinical trial.

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A Phase 2 interventional study of APG-157 and Bevacizumab in recurrent high-grade glioma. Evaluating the effectiveness of a new drug, APG-157, in combination ...

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clinicaltrials.gov/study/NCT05551013

Treatment of Recurrent GBM With APG-157 Via Expanded ...

This expanded access request will evaluate APG-157, a botanical drug under development for other cancers, as potential treatment for recurrent Glioblastoma ...

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APG-157 was administered either as monotherapy or in combination with temozolomide or tumor-treating fields. Adverse events were assessed at each study visit.