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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of radiation therapy for individuals whose brain tumors have recurred after previous treatment. Researchers aim to determine the optimal radiation dose to maximize cancer cell destruction while monitoring for side effects. Some participants may also receive bevacizumab, a targeted therapy, alongside radiation to assess its potential benefits. Individuals who had a brain tumor treated with radiation at least six months ago and have imaging confirming the cancer's return may qualify for this study. As an unphased trial, this study provides patients the chance to contribute to groundbreaking research that could enhance future treatment options.

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.

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

Research has shown that radiation therapy for brain tumors is generally safe. Various delivery methods can effectively control tumors while protecting healthy brain tissue. For example, one study found that stereotactic radiosurgery, a precise type of radiation therapy, is safe and positively affects thinking skills.

Regarding bevacizumab, a drug often used for brain cancer, studies suggest it is also safe. In a review of nearly 1,000 patients with recurring glioblastoma (a type of brain tumor), bevacizumab helped manage the disease. Another study found that combining bevacizumab with radiation therapy was safe.

Overall, both radiation therapy and bevacizumab have been well-tolerated by people with brain tumors. While all treatments can have side effects, these treatments have shown a good safety record in previous studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of radiation therapy with bevacizumab for recurrent brain cancer because it offers a potential new approach to tackling this challenging condition. Unlike standard treatments that typically focus on either chemotherapy or radiation alone, bevacizumab is an antibody that targets and inhibits VEGF, a protein that promotes blood vessel growth in tumors. By combining bevacizumab with radiation, this treatment aims to enhance the effectiveness of radiation by starving the tumor of the blood supply it needs to grow. This dual approach could potentially improve outcomes for patients by making tumors more susceptible to radiation.

What evidence suggests that this trial's treatments could be effective for recurrent brain cancer?

This trial will compare two treatment approaches for recurrent brain cancer. In one arm, participants will receive radiation therapy with conventional fractionation. Research has shown that radiation therapy can effectively treat brain tumors like glioblastoma, and using standard radiation doses with techniques such as intensity-modulated radiation therapy (IMRT) can extend the lives of patients with aggressive brain tumors. However, for recurrent tumors, the outlook is generally less positive, with average survival times of less than five months.

In the other arm, participants will receive both radiation therapy and bevacizumab. Studies have found that bevacizumab is helpful for treating recurrent glioblastoma, offering about 4.2 months where the disease does not worsen. It can delay disease progression and improve symptoms. While bevacizumab does not significantly increase overall survival time, it can enhance quality of life by reducing symptoms. ^{1 5 6 7 8}

Who Is on the Research Team?

Susan McGovern, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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

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

I can do most activities but may need help.

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

Exclusion Criteria

Pregnancy

My condition is recurrent DIPG.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

Citations

1. avastin.com avastin.com/hcp/rgbm/efficacy-data.html

Avastin® (bevacizumab) Clinical Trials | rGBM Treatment Recurrent Glioblastoma: Avastin Efficacy Data. Avastin is indicated for the treatment of recurrent glioblastoma in adults.

2. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-023-11043-6

Use of Bevacizumab in recurrent glioblastoma - BMC Cancer Patients with rGBM could gain benefits in PFS, palliative, and cognitive advantages from BEV treatment, although the OS benefits could not be verified with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01269853

Study Details | NCT01269853 | Repeated Super-selective ... We have recently completed a Phase I clinical trial that has shown that SIACI of Bevacizumab is safe and effective up to a dose of 15mg/kg in patients with ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5581989/

Clinical Outcomes in Recurrent Glioblastoma with ... A previous review (995 patients) estimated a progression free survival (PFS) on BEV of 4.2 months (SD±2.1) with an overall survival (OS) after progression on ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12106581/

Bevacizumab in recurrent glioblastoma: dose matter? In conclusion, this retrospective study confirms the role of bevacizumab as a useful treatment strategy in recurrent glioblastoma. Our data ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4436682/

Clinical outcomes with bevacizumab-containing and non ... This analysis evaluated the efficacy and safety of bevacizumab as monotherapy and with irinotecan for recurrent glioblastoma in community-based practices.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01332929

Safety Evaluation of a Combination of Brain Radiation ... This phase I pilot study aims to define the safety of a combined treatment of bevacizumab and whole brain radiation therapy for the treatment of patients ...

8. avastin.com avastin.com/patient/rgbm/treatment/benefits-risks.html

Benefits and Risks of Treatment for recurrent gliobastoma ... View benefits and risks of Avastin® (bevacizumab) treatment for recurrent glioblastoma (rGBM). See full safety for more information.