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

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.

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.

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. ^{1 2 3 4 5}

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. ^{2 6 7 8 9}

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. ^{2 5 6 9 10}

Research Team

Nicole Shonka, MD

Principal Investigator

University of Nebraska

Joon Uhm, MD

Principal Investigator

Mayo Clinic

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 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 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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of bevacizumab in patients with recurrent brain tumours: A population-based evaluation. [2022]

2. United States 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Role of a second chemotherapy in recurrent malignant glioma patients who progress on bevacizumab. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas--a Pediatric Brain Tumor Consortium study. [2022]

5. England 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. [2021]

6. China pubmed.ncbi.nlm.nih.gov

[Preliminary clinical evaluations of bevacizumab for recurrent malignant glioma in Chinese patients]. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Bevacizumab use for recurrent high-grade glioma at McGill University Hospital. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bevacizumab in active brain metastases from non-small cell lung cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Genetic modification of neurons to express bevacizumab for local anti-angiogenesis treatment of glioblastoma. [2018]