Proton Therapy + Avastin for Recurrent Glioblastoma

Recruiting in Palo Alto (17 mi)

Overseen by Eric A. Mellon

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

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

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this research is to find hidden cancer with an experimental magnetic resonance imaging (MRI) scan called spectroscopic magnetic resonance imaging (sMRI). That spectroscopic MRI scan will be used to increase the area of the brain receiving radiation and then the dose of radiation in attempt to kill more of the cancer. Proton radiotherapy and bevacizumab (Avastin) are used to minimize the possible side effects of this approach.

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.

What data supports the effectiveness of the treatment Proton Therapy + Avastin for Recurrent Glioblastoma?

Proton therapy is known to reduce off-target irradiation in brain tumors, which may help protect healthy brain tissue while treating glioblastoma. Additionally, intensity-modulated proton therapy (IMPT) has shown promise in improving target conformity and reducing unnecessary exposure to critical tissues in other cancers, suggesting potential benefits for glioblastoma treatment. ^{1 2 3 4 5}

Is proton therapy safe for humans?

Proton therapy, including intensity-modulated proton therapy (IMPT), has been studied for various cancers like liver, esophageal, head and neck, and lung cancer. It generally shows promise in reducing damage to normal tissues compared to traditional radiation, suggesting it is relatively safe for humans. ^{2 6 7 8 9}

How is the treatment Proton Therapy + Avastin for Recurrent Glioblastoma different from other treatments?

Proton therapy, used in this treatment, is unique because it can target tumors more precisely than traditional radiation, reducing damage to surrounding healthy tissue and potentially preserving quality of life. This is particularly important for recurrent glioblastoma, a highly aggressive brain tumor, where minimizing side effects is crucial. ^{2 3 4 10 11}

Research Team

Eric A. Mellon

Principal Investigator

University of Miami

Eligibility Criteria

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.

Total area of recurrence on MRI must have a linear maximum measurement of 6 cm or less

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.

Trial Timeline

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

Treatment Details

Interventions

• Bevacizumab (Monoclonal Antibodies)
• Intensity Modulated Proton Therapy (IMPT) (Proton Beam Therapy)

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.

Participant Groups

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Miami Miami, FL

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Patients Recruited

423,000+

References

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

Clinical implementation of intensity modulated proton therapy for thoracic malignancies. [2022] Intensity modulated proton therapy (IMPT) can improve dose conformality and better spare normal tissue over passive scattering techniques, but range uncertainties complicate its use, particularly for moving targets. We report our early experience with IMPT for thoracic malignancies in terms of motion analysis and management, plan optimization and robustness, and quality assurance.

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

Clinical outcomes of intensity modulated proton therapy and concurrent chemotherapy in esophageal carcinoma: a single institutional experience. [2022] Intensity-modulated proton therapy (IMPT) is an emerging advanced radiation technique. Although dosimetric studies demonstrate the superiority of IMPT for improving target conformity and reducing unnecessary dose to critical normal tissues, clinical experience is limited. We aim to describe our preliminary experience implementing IMPT concurrently with chemotherapy in esophageal carcinoma (EC).

3. United States 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. [2022] There are very little data available comparing outcomes of intensity-modulated proton therapy (IMPT) to intensity-modulated radiation therapy (IMRT) in patients with locally advanced NSCLC (LA-NSCLC).

4. China pubmed.ncbi.nlm.nih.gov

Proton radiotherapy for glioma and glioblastoma. [2023] Radiotherapy (RT) continues to be an important component of treatment of glioma, particularly high-grade glioma and glioblastoma multiforme (GBM). GBM is one of the most aggressive central nervous system (CNS) tumors, with high rates of recurrence and very low rates of long-term survival. However, outcomes in these patients are improving with modern genetic profiling and multimodal therapy, which leads to more consideration for the risk for toxicities associated with traditional photon-based RT. Proton therapy (PT) is an increasingly available method to reduce off-target irradiation in CNS tumors due to the intrinsic properties of heavy-particle irradiation. Here, we review currently available data examining the used of PT in glioma patients, including dose escalation for GBM, re-irradiation (reRT) of recurrent glioma, and the potential cognitive sparing effects of conventional dose PT. We discuss the incorporation of PT into the multimodal therapy of GBM patients, and how the aggressive nature of the disease poses a unique challenge to PT study design. We also describe how PT may provide the most feasible method for implementing high rate 'FLASH' RT and the implications for glioma patients. We conclude with a discussion of ongoing clinical trials, the necessity of continued research, and how we interpret and incorporate available data into our current practice.

5. United States 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. [2022] Intensity modulated proton therapy (IMPT) could yield high linear energy transfer (LET) in critical structures and increased biological effect. For head and neck cancers at the skull base this could potentially result in radiation-associated brain image change (RAIC). The purpose of the current study was to investigate voxel-wise dose and LET correlations with RAIC after IMPT.

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

Proton radiation therapy for head and neck cancer. [2018] Due to the close spatial relationship of head and neck and skull base tumors to numerous normal anatomical structures, conventional photon radiation therapy can be associated with significant acute and long-term treatment-related toxicities. Superior dose localization properties of proton radiation therapy allow smaller volumes of normal tissues to be irradiated than is feasible with any photon technique. Intensity-modulated proton therapy (IMPT) is a powerful delivery technique which results in improved dose distribution as compared to that of intensity-modulated radiation therapy (IMRT). Initial clinical experience with proton radiation therapy in treatment of head and neck and skull base tumors is promising. Prospective multi-institutional trials are underway to define the role of proton radiation therapy, particularly IMPT, in the treatment of head and neck and skull base tumors.

7. United States 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. [2023] Intensity-modulated proton therapy (IMPT) has the potential to reduce radiation dose to normal organs when compared to intensity-modulated radiation therapy (IMRT). We hypothesized that IMPT is associated with a reduced rate of cardiopulmonary toxicities in patients with Stage III NSCLC when compared with IMRT.

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

Intensity Modulated Proton Therapy for Hepatocellular Carcinoma: Initial Clinical Experience. [2022] Our purpose was to assess the safety and efficacy of intensity modulated proton therapy (IMPT) for the treatment of hepatocellular carcinoma (HCC).

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

Intensity-modulated proton therapy for nasopharyngeal carcinoma: Decreased radiation dose to normal structures and encouraging clinical outcomes. [2022] Intensity-modulated proton therapy (IMPT) has the potential to spare dose to organs at risk (OAR) when compared to intensity-modulated radiotherapy (IMRT) while maintaining excellent clinical outcomes.

10. England pubmed.ncbi.nlm.nih.gov

Functional image-guided dose escalation in gliomas using of state-of-the-art photon vs. proton therapy. [2018] Label="BACKGROUND" NlmCategory="BACKGROUND">Recurrences of glioma are usually local, suggesting the need for higher tumor dose. We investigated the boundaries for dose escalation of an 18F-fluoro-ethyl-tyrosine positron emission tomography defined target by intensity-modulated photon therapy (IMRT), volumetric modulated arc therapy (VMAT) and intensity-modulated proton therapy (IMPT).

11. Germany pubmed.ncbi.nlm.nih.gov

Proton therapy re-irradiation preserves health-related quality of life in large recurrent glioblastoma. [2020] Proton therapy could minimize the risk of side effects and, therefore, reduce the possible detrimental effect on health-related quality of life (HRQOL) of re-irradiation. The aim of this study was to determine the effect of re-irradiation with active scanning proton therapy on recurrent glioblastoma (GBM) in terms of HRQOL scored by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and EORTC Quality of Life Questionnaire Brain Cancer Module (QLQ-BN20).