Radiation Therapy + Bevacizumab for Recurrent Brain Cancer

Overseen By Susan L. McGovern, MD, PHD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Chemotherapy

Disqualifiers: Recurrent DIPG, Pregnancy, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot clinical trial studies the side effects and best dose of radiation therapy in patients with brain tumors that have come back after previous treatment with radiation therapy. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radiation therapy in different ways may kill more tumor cells.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take chemotherapy drugs during the trial, except for temozolomide or bevacizumab, if your doctor approves.

What data supports the effectiveness of the treatment Radiation Therapy + Bevacizumab for Recurrent Brain Cancer?

Research shows that stereotactic radiotherapy (SRT) can better preserve quality of life compared to whole-brain radiotherapy for patients with brain metastases, and reirradiation with SRT has shown promising results in improving survival and managing symptoms with minimal side effects. ^{1 2 3 4 5}

Is the combination of radiation therapy and bevacizumab generally safe for humans?

Bevacizumab, when combined with radiation therapy, has been used to treat complications like adverse radiation effects and radiation necrosis in the brain. However, it has been associated with risks such as stroke, bleeding, and wound-healing issues, especially in highly vascular tumors like glioblastoma. ^{6 7 8 9 10}

How is the treatment of Radiation Therapy + Bevacizumab for recurrent brain cancer different from other treatments?

This treatment combines radiation therapy with bevacizumab, a drug that targets and inhibits a protein called VEGF, which helps tumors grow new blood vessels. This combination has shown promise in improving outcomes for patients with recurrent brain cancer, especially when previous treatments have failed, by potentially enhancing the effectiveness of radiation and reducing complications like radiation necrosis. ^{11 12 13 14 15}

Research Team

Susan McGovern, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with brain tumors that have returned after previous radiation therapy. Eligible participants must have had only one prior round of radiation, may have undergone surgery before re-radiation, and should not be pregnant or have recurrent diffuse intrinsic pontine glioma (DIPG). They need a performance status score of 50-100 and recent imaging showing recurrent disease.

Inclusion Criteria

Signed informed consent by patient and/or parents or legal guardian

I have had one round of brain radiation at a specific dose.

I can do most activities but may need help.

Exclusion Criteria

Pregnancy

My condition is recurrent DIPG.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo radiation therapy with conventional fractionation and dose constraints for up to 6 weeks

6 weeks

Weekly visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

1 visit at 1 month, then every 2 months for 1 year, then every 3 months for 1 year

Treatment Details

Interventions

• Quality-of-Life Assessment
• Radiation Therapy

Trial Overview The study tests the side effects and optimal dose of re-administering radiation therapy to treat recurring brain tumors. It explores whether different methods of delivering radiation can more effectively kill tumor cells. Bevacizumab may also be used at the treating neuro-oncologist's discretion.

Participant Groups

Group I: Arm I (conventional fractionation) Experimental Treatment 2 Interventions

Patients undergo radiation therapy with conventional fractionation and dose constraints. Treatment continues for up to 6 weeks in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (conventional fractionation, bevacizumab) Active Control 3 Interventions

Patients undergo radiation therapy with conventional fractionation and dose constraints. Patients also receive bevacizumab concurrently at the discretion of the treating neuro-oncologist. Treatment continues for up to 6 weeks in the absence of disease progression or unacceptable toxicity.

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a randomized trial involving 20 patients with multiple brain metastases, stereotactic radiotherapy (SRT) was found to significantly preserve quality of life (QoL) compared to whole-brain radiotherapy (WBRT), particularly in mobility, self-care, and alopecia after 3 months.

Patients receiving SRT reported better physical and social functioning, indicating that SRT not only controls local tumors but also enhances the overall well-being of patients compared to traditional WBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life among patients with 4 to 10 brain metastases after treatment with whole-brain radiotherapy vs. stereotactic radiotherapy: a phase III, randomized, Dutch multicenter trial. Hartgerink, D., Bruynzeel, A., Eekers, D., et al.[2022]

The review discusses various treatment options for newly diagnosed and recurrent brain metastases, including whole-brain radiotherapy, radiosurgery, and chemotherapy, highlighting the importance of tailoring treatments to specific patient prognostic subgroups.

Emerging therapies, such as new radiosensitizers and cytotoxic agents, are being explored to improve local control and survival rates while managing the risk of late neurotoxicity associated with these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy and chemotherapy of brain metastases. Soffietti, R., Costanza, A., Laguzzi, E., et al.[2018]

Reirradiation for patients with brain metastases can effectively alleviate symptoms and improve survival rates, with minimal late neurotoxicity, making it a valuable treatment option that is often underutilized.

Recent studies indicate that stereotactic radiosurgery, in addition to traditional whole brain radiotherapy, offers promising results for reirradiation, enhancing treatment options for patients with recurrent brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reirradiation for progressive brain metastases. Bahl, A., Kumar, M., Sharma, DN., 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 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]

References

1. China pubmed.ncbi.nlm.nih.gov

Quality of life among patients with 4 to 10 brain metastases after treatment with whole-brain radiotherapy vs. stereotactic radiotherapy: a phase III, randomized, Dutch multicenter trial. [2022]

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

Radiotherapy and chemotherapy of brain metastases. [2018]

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

Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline. [2023]

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

Phase I trial of simultaneous in-field boost with helical tomotherapy for patients with one to three brain metastases. [2022]

5. India pubmed.ncbi.nlm.nih.gov

Reirradiation for progressive brain metastases. [2022]

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

Bevacizumab for the treatment of post-stereotactic radiosurgery adverse radiation effect. [2020]

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

Evaluation of acute locoregional toxicity in patients with breast cancer treated with adjuvant radiotherapy in combination with bevacizumab. [2019]

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

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

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

Bevacizumab for the Treatment of Gammaknife Radiosurgery-Induced Brain Radiation Necrosis. [2022]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

Clinical Experience of Bevacizumab for Radiation Necrosis in Patients with Brain Metastasis. [2020]

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

The role of salvage reirradiation for malignant gliomas that progress on bevacizumab. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Bevacizumab for radiation necrosis following radiotherapy of brain metastatic disease: a systematic review & meta-analysis. [2021]

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

Hypofractionated Radiosurgery Plus Bevacizumab for Locally Recurrent Brain Metastasis with Previously High-Dose Irradiation. [2020]

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

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

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

Bevacizumab vs laser interstitial thermal therapy in cerebral radiation necrosis from brain metastases: a systematic review and meta-analysis. [2022]