Proton Therapy + Avastin for Recurrent Glioblastoma

Overseen By Eric A. Mellon

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Miami

Must be taking: Bevacizumab

Must not be taking: Anticoagulants, Chemotherapy

Disqualifiers: Other brain tumors, Pregnancy, Severe comorbidities, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

96 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to treat recurrent glioblastoma, an aggressive brain cancer, by using a special MRI scan to target cancer more precisely with radiation. It combines proton therapy (Intensity Modulated Proton Therapy, or IMPT) with the drug Avastin (Bevacizumab) to reduce side effects while aiming to kill more cancer cells. The trial includes two groups, each testing different radiation doses. This study may suit individuals whose glioblastoma has returned after previous treatment, especially if their MRI shows growth outside the original treatment area. As an unphased trial, it offers a unique opportunity to explore innovative treatment combinations for recurrent glioblastoma.

Will I have to stop taking my current medications?

The trial requires a minimum time to pass after taking certain medications before starting the study treatment. For example, 28 days must pass after taking most experimental or cytotoxic agents, but only 14 days for vincristine and 21 days for procarbazine and Temozolomide. The protocol does not specify other medication restrictions, so it's best to discuss your current medications with the study team.

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

Research has shown that Intensity Modulated Proton Therapy (IMPT) offers a promising approach for treating brain tumors like glioblastoma. It helps protect healthy brain tissue and reduces the risk of cognitive issues, potentially improving patients' quality of life while effectively controlling cancer.

Studies have found that Bevacizumab (brand name Avastin) is approved for treating recurrent glioblastoma. Most patients tolerate it well, though some may experience side effects such as high blood pressure, nosebleeds, and fatigue. Serious side effects occur less frequently.

Both treatments have demonstrated promise in clinical settings, providing a good balance between effectiveness and safety. Participants in trials should discuss any concerns with their healthcare team to understand how these treatments might affect them personally. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Intensity Modulated Proton Therapy (IMPT) combined with Bevacizumab for recurrent glioblastoma because it offers a more precise and potentially less harmful radiation treatment. Unlike traditional radiation therapies, which can affect both healthy and cancerous tissues, IMPT targets tumors with pinpoint accuracy, minimizing damage to surrounding healthy brain tissue. Additionally, the integration of Bevacizumab, an anti-angiogenic drug, helps inhibit the growth of blood vessels that supply the tumor, potentially enhancing the effectiveness of the treatment. Together, these approaches aim to improve outcomes by reducing side effects and potentially extending survival in a challenging-to-treat cancer.

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

Research has shown that Intensity Modulated Proton Therapy (IMPT) effectively treats gliomas, including glioblastoma. IMPT minimizes harm to healthy brain tissue, helping maintain brain function and quality of life. Studies indicate that it provides survival outcomes as good as or better than other radiation treatments. In this trial, participants in both Cohort A and Cohort B will receive IMPT at different dosage levels. Additionally, Bevacizumab (Avastin) is used for recurrent glioblastoma and has been shown to improve the time during and after treatment when the cancer doesn't worsen by an average of 4.2 months. While it doesn't increase overall survival time, it remains a helpful option for managing symptoms and slowing disease progression. Participants in both cohorts will also receive Bevacizumab per standard of care. ^{1 6 7 8 9}

Who Is on the Research Team?

Jonathan Bell, MD, PhD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

Adults with recurrent glioblastoma who've had prior brain radiation, can undergo MRI scans, and have a life expectancy of over 12 weeks. They must not be pregnant or breastfeeding and agree to use contraception. Excluded are those with multi-focal disease across multiple lobes, previous Bevacizumab treatment, certain unstable health conditions, or recent major surgeries.

Inclusion Criteria

Liver function tests within 21 days prior to registration

My condition is recurrent glioblastoma or a similar type.

I finished brain radiation treatment at least 4-6 months ago.

Exclusion Criteria

Pregnant or breastfeeding patients

I am not pregnant and willing to use contraception if of childbearing potential.

My glioma has not been treated with standard first-line therapies.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Participants receive sMRI-guided radiation therapy with proton therapy and bevacizumab

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Regular visits as per protocol

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Intensity Modulated Proton Therapy (IMPT)

Trial Overview The trial tests an experimental MRI technique (sMRI) to better target proton radiotherapy for recurrent glioblastoma. It also evaluates the safety and effectiveness of adding Bevacizumab (Avastin) to minimize side effects from this intensified treatment approach.

How Is the Trial Designed?

Group I: Cohort B: sMRI-Guided RT at 40 Gy in 10 fractions Experimental Treatment 2 Interventions

Participants will receive a total dose of 4000 cGY (40Gy) of Spectroscopic Magnetic Resonance Imaging (sMRI)-guided radiation therapy delivered in 10 fractions, 400 cGy (4 Gy) to the Clinical Target Volume (CTV) by Intensity Modulated Proton Therapy (IMPT) simultaneous integrated boost technique. Participants will also receive Bevacizumab per standard of care, at treating physician's discretion. Initial dose will begin prior to first dose of radiation therapy (RT).

Group II: Cohort A: sMRI-Guided RT at 35 Gy in 10 fractions Experimental Treatment 2 Interventions

Participants will receive a total dose of 3500 centigrays (cGY) (35Gy) of Spectroscopic Magnetic Resonance Imaging (sMRI)-guided radiation therapy delivered in 10 fractions, 350 cGy (3.5 Gy) to the Clinical Target Volume (CTV) by Intensity Modulated Proton Therapy (IMPT) simultaneous integrated boost technique. Participants will also receive Bevacizumab per standard of care, at treating physician's discretion. Initial dose will begin prior to first dose of radiation therapy (RT).

Intensity Modulated Proton Therapy (IMPT) is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Intensity Modulated Proton Therapy for:

• Various cancers including brain tumors, prostate cancer, pediatric cancers

Approved in European Union as Intensity Modulated Proton Therapy for:

• Various cancers including brain tumors, prostate cancer, pediatric cancers

Approved in Japan as Intensity Modulated Proton Therapy for:

• Various cancers including brain tumors, prostate cancer, pediatric cancers

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Published Research Related to This Trial

Proton therapy (PT) offers a promising alternative to traditional photon-based radiotherapy for glioblastoma multiforme (GBM) patients by potentially reducing off-target irradiation and associated toxicities, which is crucial given the aggressive nature of this tumor.

Current research suggests that PT may enhance treatment outcomes for glioma patients, particularly in terms of cognitive sparing and the feasibility of high-rate 'FLASH' radiotherapy, highlighting the need for ongoing clinical trials to further evaluate its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiotherapy for glioma and glioblastoma. Goff, KM., Zheng, C., Alonso-Basanta, M.[2023]

Intensity modulated proton therapy (IMPT) was successfully used in 34 patients with lung and mediastinal cancers, showing significant improvements in sparing normal tissues compared to both intensity modulated radiation therapy (IMRT) and passive scattering proton therapy (PSPT).

IMPT achieved lower doses to critical organs like the lungs and heart while maintaining higher doses to the tumor, demonstrating effective motion management and robust treatment planning through advanced 4D CT simulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical implementation of intensity modulated proton therapy for thoracic malignancies. Chang, JY., Li, H., Zhu, XR., et al.[2022]

Re-irradiation with active scanning proton therapy in 33 patients with recurrent glioblastoma showed improvements or stability in most health-related quality of life (HRQOL) domains, indicating it is a safe and effective treatment option.

Patients experienced significant improvements in global health, social functioning, and motor function over time, while cognitive and emotional functioning remained stable, suggesting that proton therapy helps preserve HRQOL during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton therapy re-irradiation preserves health-related quality of life in large recurrent glioblastoma. Scartoni, D., Amelio, D., Palumbo, P., et al.[2020]

Proton radiation therapy, particularly intensity-modulated proton therapy (IMPT), offers better dose localization compared to conventional photon radiation therapy, potentially reducing damage to surrounding healthy tissues in patients with head and neck and skull base tumors.

Initial clinical experiences suggest that IMPT may lead to fewer acute and long-term toxicities, and ongoing multi-institutional trials aim to further establish its effectiveness in treating these complex tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiation therapy for head and neck cancer. Chan, AW., Liebsch, NJ.[2018]

Intensity modulated proton therapy (IMPT) demonstrated a high local control rate of 94% and an overall survival rate of 78% in a study of 37 patients with hepatocellular carcinoma (HCC) over a median follow-up of 21 months.

The treatment was found to be safe, with only 3% of patients experiencing significant acute toxicity, and 16% showing a minor increase in liver function scores, indicating that IMPT is a feasible option for HCC management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity Modulated Proton Therapy for Hepatocellular Carcinoma: Initial Clinical Experience. Bhangoo, RS., Mullikin, TC., Ashman, JB., et al.[2022]

Intensity-modulated proton therapy (IMPT) showed significant dosimetric advantages over intensity-modulated radiotherapy (IMRT) in sparing adjacent organs at risk (OAR) in 15 out of 29 OAR for 10 patients with nasopharyngeal carcinoma.

With a median follow-up of 24.5 months, IMPT achieved a 100% locoregional control rate and an 88.9% overall survival rate, suggesting excellent clinical outcomes that warrant further investigation into potential reductions in toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated proton therapy for nasopharyngeal carcinoma: Decreased radiation dose to normal structures and encouraging clinical outcomes. Lewis, GD., Holliday, EB., Kocak-Uzel, E., et al.[2022]

In a study of 79 patients with locally advanced non-small cell lung cancer (LA-NSCLC), intensity-modulated proton therapy (IMPT) showed similar overall survival rates compared to intensity-modulated radiation therapy (IMRT) after one year, with rates of 68% for IMPT and 65% for IMRT.

Both treatment methods resulted in low rates of severe toxicities, with only 15% of IMPT and 9% of IMRT patients experiencing grade 3 or 4 toxicities three months post-treatment, indicating that IMPT is as safe as IMRT in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Outcomes of Patients With Locally Advanced Non-small Cell Lung Cancer Treated With Intensity-Modulated Proton Therapy Versus Intensity-Modulated Radiation Therapy: The Mayo Clinic Experience. Yu, NY., DeWees, TA., Liu, C., et al.[2022]

In a study of 15 patients with radiation-associated brain image change (RAIC) after intensity modulated proton therapy (IMPT), a significant correlation was found between the dose of radiation and the linear energy transfer (LETd), indicating that higher LETd may increase the risk of RAIC.

The analysis showed that for patients receiving higher doses (60 to 70 Gy), the probability of developing RAIC increased with LETd, suggesting that assessing LETd in treatment plans could be clinically important to minimize potential brain damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mixed Effect Modeling of Dose and Linear Energy Transfer Correlations With Brain Image Changes After Intensity Modulated Proton Therapy for Skull Base Head and Neck Cancer. Engeseth, GM., He, R., Mirkovic, D., et al.[2022]

Intensity-modulated proton therapy (IMPT) combined with chemotherapy showed a high clinical complete response rate of 84% in 19 patients with esophageal carcinoma, indicating its efficacy in treating this type of cancer.

With a median follow-up of 17 months, patients experienced a median overall survival of 39.2 months, and the treatment was associated with acceptable levels of acute toxicity, primarily esophagitis and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of intensity modulated proton therapy and concurrent chemotherapy in esophageal carcinoma: a single institutional experience. Prayongrat, A., Xu, C., Li, H., et al.[2022]

In a study involving seven patients, dose escalation for glioma treatment was successfully achieved using IMRT, VMAT, and IMPT, with IMPT showing the highest boost dose of 85.1 GyE.

IMPT not only reduced the overdose volume and the risk of radionecrosis significantly compared to IMRT and VMAT, but it also maintained safety by respecting normal tissue constraints, making it the most favorable option for higher tumor doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional image-guided dose escalation in gliomas using of state-of-the-art photon vs. proton therapy. Holm, AIS., Petersen, JBB., Muren, LP., et al.[2018]

In a study of 163 patients with Stage III non-small cell lung cancer (NSCLC), intensity-modulated proton therapy (IMPT) significantly reduced the risk of severe pneumonitis and cardiac events compared to intensity-modulated radiation therapy (IMRT).

IMPT demonstrated better dosimetric sparing of the lungs and heart without compromising overall survival or tumor control, making it a potentially safer treatment option for patients with poor pre-treatment lung function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiopulmonary Toxicity Following Intensity-Modulated Proton Therapy (IMPT) Versus Intensity-Modulated Radiation Therapy (IMRT) for Stage III Non-Small Cell Lung Cancer. Yu, NY., DeWees, TA., Voss, MM., et al.[2023]

Citations

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Use of Bevacizumab in recurrent glioblastoma - BMC Cancer A phase II trial found that BEV plus ONA improved OS in patients with rGBM having unmethylated MGMT (mOS, ONA + BEV vs. PLA + BEV, 10.9 vs. 7.5 ...

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DATA FROM A PHASE II CLINICAL TRIAL - PMC Treatment with the combination of bevacizumab and TTFields in patients with recurrent GBM is safe and feasible and has shown clinical efficacy. Articles ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01269853

Study Details | NCT01269853 | Repeated Super-selective ... A single Super-selective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab (up to 15mg/kg) is safe and effective in the treatment of recurrent GBM.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0967586819321721

Impact of adverse events of bevacizumab on survival ... Our results indicate that the development of AEs to bevacizumab or bevacizumab-containing regimens is associated with unfavorable glioma-related survival ...