Nivolumab + Radiation + Bevacizumab for Glioblastoma

Recruiting at 12 trial locations

Overseen By Christian Grommes, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Anti-CTLA-4, Anti-PD-1

Disqualifiers: Heart failure, Hypertension, Autoimmune, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

39 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on high doses of corticosteroids or have been treated with certain immune therapies before, you may not be eligible to participate.

What data supports the effectiveness of the drug Bevacizumab when used with radiation for glioblastoma?

Research suggests that Bevacizumab, when combined with radiation, may improve the response of gliomas (a type of brain tumor) to treatment by targeting VEGF (a protein that helps tumors grow blood vessels). Some studies have shown that adding Bevacizumab to standard treatments can prolong the time before the disease worsens, although it may not extend overall survival. ^{1 2 3 4 5}

Is the combination of Nivolumab, Radiation, and Bevacizumab safe for humans?

Bevacizumab, when combined with radiation and other treatments, has been linked to risks like stroke, bleeding, and wound-healing problems, especially in brain tumors. However, studies have shown that adding Bevacizumab to radiation therapy and temozolomide for glioblastoma is generally associated with minimal toxicity. ^{1 3 6 7 8}

How is the treatment with Nivolumab, Radiation, and Bevacizumab for glioblastoma different from other treatments?

This treatment is unique because it combines Nivolumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with Bevacizumab, which reduces blood vessel growth in tumors, and radiation therapy. This combination aims to enhance the body's immune response while also targeting the tumor's blood supply, which is different from standard treatments that typically involve chemotherapy and radiation alone. ^{6 7 8 9 10}

What is the purpose of this trial?

This study is being done to see if adding nivolumab to radiation therapy and bevacizumab can increase the effectiveness of the treatment for recurrent glioblastoma.

Research Team

Christian Grommes, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with confirmed grade IV glioblastoma, IDH wildtype, MGMT hypermethylation, who've had surgery and chemo with temozolomide followed by radiation. They must show signs of recurrence but have a relatively small tumor (≤5cm), good performance status, and normal organ function. Excluded are those with multiple recurrences, certain heart conditions or infections, active autoimmune diseases requiring recent treatment, pregnancy/breastfeeding intentions within trial period, MRI incompatibility or prior treatments conflicting with the study drugs.

Inclusion Criteria

I have been treated with radiation and temozolomide.

My liver is working well.

Platelet count ≥ 100,000/mm3

Exclusion Criteria

Prior spontaneous CNS hemorrhage (as determined from clinical history, CT, or MRI)

I have had a blood clot in my lung or leg in the last 2 months.

Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab in combination with hypofractionated re-irradiation and bevacizumab

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Bevacizumab
• Nivolumab
• Re-irradiation (RT)
• Re-resection

Trial Overview The trial tests if adding nivolumab to standard re-irradiation therapy and bevacizumab improves outcomes for recurrent glioblastoma patients. It's exploring whether this combination can better control tumor growth compared to current methods.

Participant Groups

Group I: Recurrent Glioblastoma, Surgery Experimental Treatment 4 Interventions

The second cohort is for patients with recurrent GBM who are undergoing surgery as part of their treatment.

Group II: Recurrent Glioblastoma, No Surgery Experimental Treatment 3 Interventions

One cohort is for patients with recurrent GBM who are not undergoing surgical debulking as part of their treatment plan

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

In a study involving 25 patients with recurrent glioblastoma and anaplastic gliomas, the combination of bevacizumab and hypofractionated stereotactic radiotherapy (HFSRT) was found to be safe and well tolerated, with no cases of radiation necrosis reported.

The treatment showed promising efficacy, with a 50% overall response rate and a median overall survival of 12.5 months, indicating that this regimen could be an effective option for patients with recurrent malignant gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. Gutin, PH., Iwamoto, FM., Beal, K., et al.[2022]

In a retrospective analysis of the AVAglio trial involving 921 glioblastoma patients, those with IDH1 wild-type proneural tumors showed a significant overall survival (OS) benefit from bevacizumab treatment compared to placebo, with an OS of 17.1 months versus 12.8 months.

While patients with mesenchymal and proneural tumors experienced progression-free survival (PFS) benefits from bevacizumab, only the proneural subtype demonstrated a corresponding OS advantage, highlighting the importance of molecular subtypes in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Sandmann, T., Bourgon, R., Garcia, J., et al.[2022]

In a Phase II pilot study involving 10 patients with newly diagnosed glioblastoma, the combination of bevacizumab (BV), temozolomide (TMZ), and regional radiation therapy (RT) showed acceptable safety and tolerability, with some patients experiencing serious toxicities like presumed radiation-induced optic neuropathy and high rates of fatigue and myelotoxicity.

Preliminary results indicated encouraging mean progression-free survival, but further research with more patients and longer follow-up is needed before considering routine use of this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Lai, A., Filka, E., McGibbon, B., et al.[2022]

In a study involving 15 patients with high-grade glioma, the combination of bevacizumab, radiation, and temozolomide was found to be feasible, with 86.6% of patients completing the treatment regimen.

The treatment resulted in a high radiographic response rate of 92.8%, and one-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively, indicating promising efficacy in managing this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of using bevacizumab with radiation therapy and temozolomide in newly diagnosed high-grade glioma. Narayana, A., Golfinos, JG., Fischer, I., et al.[2022]

In a phase III trial involving 911 patients with newly diagnosed glioblastoma, those treated with bevacizumab had a longer safety follow-up (12.3 months) and a higher completion rate of maintenance temozolomide (64.6%) compared to placebo (36.9%).

While bevacizumab was associated with a higher incidence of adverse events such as arterial thromboembolic events (5.9% vs 1.6%) and wound-healing complications (6.9% vs 4.7%), these did not hinder patients' ability to receive standard treatment or undergo subsequent surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab, temozolomide, and radiotherapy for newly diagnosed glioblastoma: comprehensive safety results during and after first-line therapy. Saran, F., Chinot, OL., Henriksson, R., et al.[2022]

In a study of 70 patients with newly diagnosed glioblastoma, combining bevacizumab (BV) with radiation therapy (RT) and temozolomide (TMZ) resulted in improved progression-free survival (PFS) of 13.6 months compared to 7.6 months in a control group, although overall survival (OS) was similar between groups.

The presence of MGMT promoter methylation in tumor tissue was associated with better OS and PFS, suggesting that this biomarker may help identify patients who could benefit more from the treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. Lai, A., Tran, A., Nghiemphu, PL., et al.[2022]

Bevacizumab, a monoclonal antibody that targets VEGF, has been shown to reduce tumor growth and associated brain swelling in glioblastoma patients, potentially improving their quality of life and survival rates.

Despite its benefits, the review highlights the importance of understanding the potential side effects and complications of bevacizumab, as well as exploring new drug combinations to enhance its efficacy in treating glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of bevacizumab therapy in the management of glioblastoma. Peak, SJ., Levin, VA.[2021]

References

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

Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. [2022]

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

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]

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

The addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastoma. [2021]

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

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]

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

Feasibility of using bevacizumab with radiation therapy and temozolomide in newly diagnosed high-grade glioma. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Bevacizumab, temozolomide, and radiotherapy for newly diagnosed glioblastoma: comprehensive safety results during and after first-line therapy. [2022]

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

Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed glioblastoma multiforme. [2018]

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

Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Ipilimumab and Bevacizumab in Glioblastoma. [2023]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Role of bevacizumab therapy in the management of glioblastoma. [2021]