PRDR + Bevacizumab for Brain Tumor

Overseen By Diana Trask, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Wisconsin, Madison

Must be taking: Bevacizumab

Disqualifiers: Pregnant, Uncontrolled hypertension, Prior malignancy, others

Stay on Your Current Meds You can continue your current medications while participating

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating certain brain tumors called high-grade gliomas. It combines a special type of radiation, Pulse Reduced Dose Rate (PRDR), with the drug bevacizumab (also known as Avastin). Researchers aim to evaluate the effectiveness of this combination for patients whose tumors have returned after standard treatments. Suitable candidates for this trial have a confirmed diagnosis of grade III or IV glioma, have experienced a recurrence, and have previously received radiation and temozolomide. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that using Pulse Reduced Dose Rate (PRDR) radiation with bevacizumab might be safe for people with brain tumors. In one study, most patients tolerated the treatment well without major safety issues. Bevacizumab, a drug already used for other conditions, is generally considered safe. It can help slow the decline in quality of life for patients with certain brain tumors, even if it doesn't improve it overall.

Additionally, bevacizumab is known to delay disease progression in some cases. These findings suggest that the treatment is generally well-tolerated, but discussing possible side effects with healthcare providers is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of PRDR radiation and bevacizumab for brain tumors because of its potential to enhance treatment effectiveness. Unlike the standard options, which often involve surgery, traditional radiation, and chemotherapy, this approach uses Pulsed Reduced Dose Rate (PRDR) radiation, which delivers radiation more slowly and continuously. This method may reduce damage to healthy brain tissue while effectively targeting tumor cells. Bevacizumab, an antibody that inhibits blood vessel growth in tumors, is combined with PRDR to potentially limit tumor blood supply and growth. Together, these treatments offer a promising strategy that might improve outcomes for patients with recurrent gliomas.

What evidence suggests that this trial's treatments could be effective for recurrent high grade gliomas?

Research has shown that combining bevacizumab with radiation treatments like PRDR can help manage recurring aggressive brain tumors known as high-grade gliomas. In this trial, participants will receive PRDR radiation with bevacizumab, followed by adjuvant bevacizumab until progression. One study found that this combination extended patients' lives after other treatments had been tried. Bevacizumab works by preventing tumors from receiving the blood supply they need to grow. Another study found that patients taking bevacizumab reported a better quality of life, even at lower doses. These findings suggest that the combination of PRDR and bevacizumab may be a promising option for those with recurring high-grade gliomas. ^{1 4 6 7 8}

Who Is on the Research Team?

Steve Howard, MD

Principal Investigator

University of Wisconsin, Madison

H. Ian Robins, MD, Ph.D

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

This trial is for adults over 18 with high-grade gliomas (Grade III or IV brain tumors) that have come back. They must not have used bevacizumab before, should be months past their initial radiation therapy and temozolomide treatment, and in a stable health condition as indicated by blood tests.

Inclusion Criteria

Hematology, chemistry and a urinalysis must meet protocol specified criteria

I have had radiation and temozolomide for my brain tumor.

My disease has come back, confirmed by tests or scans.

Exclusion Criteria

My blood pressure is not higher than 160/90 mmHg.

I had cancer before but was treated over a year ago and have been cancer-free since.

I have no active cancer except for non-melanoma skin cancer or cervical cancer in situ.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation and Concurrent Bevacizumab

Participants receive Pulse Reduced Dose Rate (PRDR) radiation in 27 fractions over 5.5 weeks with concurrent bevacizumab

5.5 weeks

Adjuvant Bevacizumab

Participants receive adjuvant bevacizumab until time of progression

Until progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• PRDR

Trial Overview The study is testing Pulse Reduced Dose Rate (PRDR) radiation given over 5.5 weeks with the drug bevacizumab, followed by more bevacizumab after radiation ends. Participants are divided into groups based on their tumor type and previous treatments.

How Is the Trial Designed?

Group I: Bevacizumab-naïve with recurrent IDH mutant glioma Active Control 2 Interventions

27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression

Group II: Bevacizumab-naïve with recurrent IDH wildtype high grade glioma Active Control 2 Interventions

27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression

Group III: Bevacizumab-exposed with refractory recurrent IDH wildtype high grade glioma Active Control 2 Interventions

27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression

Group IV: Bevacizumab-exposed with recurrent IDH mutant glioma Active Control 2 Interventions

27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression

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?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8655709/

Pulsed Reduced Dose Rate Radiotherapy in Conjunction With ... Eighty patients with recurrent high-grade glioma were included in this study; 47 patients received bevacizumab monotherapy (BEV), and 33 patients received pRDR ...

2. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1212714/full

Bevacizumab in recurrent WHO grades II–III glioma The management of recurrent WHO grade II-III (rGII-III) glioma is not well established. This study describes the clinical outcomes in ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0967586824000183

Effect of low-dose bevacizumab on health-related quality of ... Original Research. Effect of low-dose bevacizumab on health-related quality of life in patients with recurrent high-grade glioma: A retrospective clinical study.

4. mdpi.com mdpi.com/2072-6694/15/17/4279

Recurrent Glioblastoma: A Review of the Treatment Options This paper reviews data from different studies that have evaluated the efficacy of different forms of relapsed glioblastoma.

5. link.springer.com link.springer.com/article/10.1007/s11060-023-04524-y

Bevacizumab and gamma knife radiosurgery for first- ... This study demonstrates that the combined use of bevacizumab with concurrent stereotactic radiosurgery can have improve survival in patients with rGBM.

6. 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 ...

7. academic.oup.com academic.oup.com/noa/article/6/1/vdae073/7668086

Pulsed reduced-dose rate re-irradiation for patients with ... 69% of patients showed malignant transformation to grade 3 (38%) or grade 4 (31%) glioma. Overall survival following PRDR was 12.6 months (95% ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1308573

A Randomized Trial of Bevacizumab for Newly Diagnosed ... First-line use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. Progression-free survival was prolonged.