Optimized Proton Therapy for Pediatric Ependymoma

Recruiting at 1 trial location

Overseen By David Grosshans

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Previous brain radiation, Pregnancy, 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: 1

Duration: 6 weeks

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method of proton therapy to treat children with ependymoma, a type of brain tumor. The goal is to assess the safety and effectiveness of this treatment in targeting tumor cells while sparing healthy tissue. Known as Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy, this treatment uses a special form of radiation that may better protect the brain's normal areas. Children with ependymoma confined to the brain, without signs of spreading to the spine, may be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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 receive chemotherapy at the same time as the radiation therapy in this study.

What prior data suggests that this technique is safe for treating pediatric ependymoma?

Research shows that a new type of proton therapy, called LET optimized IMPT, is being tested for safety in children with ependymoma, a type of brain tumor. Proton therapy uses proton beams to target and destroy tumor cells while protecting nearby healthy tissue.

This study is in its early stages, so researchers are primarily assessing the treatment's safety and potential side effects. In other studies with proton therapy, most patients tolerated the treatment well, experiencing fewer side effects compared to traditional radiation treatments. This is because proton therapy can more accurately target tumors and cause less harm to surrounding healthy tissue.

While specific safety data for LET optimized IMPT in children with ependymoma is still being gathered, proton therapy in general has shown promise in being well-tolerated by patients. Potential participants should discuss any concerns with their healthcare providers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy (LET-optimized IMPT) for treating pediatric ependymoma because it offers a more targeted approach than conventional radiation therapies. Unlike traditional radiation treatments, LET-optimized IMPT tailors the energy delivery to maximize impact on tumor cells while minimizing damage to surrounding healthy tissue. This precision is particularly important for children, reducing the risk of long-term side effects and improving quality of life.

What evidence suggests that LET optimized IMPT is effective for treating pediatric ependymoma?

Research has shown that a new type of proton therapy, called LET-optimized IMPT, holds promise for treating tumors such as pediatric ependymoma. This therapy, administered to participants in this trial, uses proton beams to precisely target and destroy tumor cells while protecting surrounding healthy tissue. Studies have found that proton therapy can be more accurate than traditional radiation, potentially resulting in fewer side effects. Although specific results for LET-optimized IMPT in treating ependymoma are still being gathered, the therapy aims to improve outcomes by focusing the radiation more precisely. Early signs suggest it could effectively shrink tumors and safeguard healthy brain tissue in children. ^{1 3 4 6 7}

Who Is on the Research Team?

David R. Grosshans

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for children with a brain tumor called ependymoma, confirmed by previous tests. They should be able to perform daily activities at least half the time (Lansky score 50-100), have no tumor spread in the spine or previous brain radiation, and not be pregnant. They must also be able to undergo MRI scans and handle gadolinium contrast.

Inclusion Criteria

I can do most activities but may need help.

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

I am not receiving chemotherapy at the same time as radiation therapy.

Exclusion Criteria

I have had radiation therapy to my brain.

Inability to undergo MR imaging

I have ependymoma in my spine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LET optimized IMPT for up to 6 weeks

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

1 visit at 1 month, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy

Trial Overview

The study is testing LET Optimized IMPT, a type of precise radiation therapy that targets tumors while sparing healthy tissue. It's for kids who haven't had prior radiation and aren't on chemo during the trial. The effects on quality of life will also be assessed through questionnaires.

How Is the Trial Designed?

Group I: Treatment (LET optimized IMPT) Experimental Treatment 3 Interventions

Patients receive LET optimized IMPT for up to 6 weeks.

Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Proton Therapy for:

• Pediatric cancers
• Ocular melanomas
• Chordomas
• Chondrosarcomas

Approved in United States as Proton Therapy for:

• Pediatric cancers
• Ocular melanomas
• Chordomas
• Chondrosarcomas
• Brain tumors
• Spinal tumors

Approved in Japan as Proton Therapy for:

• Pediatric cancers
• Ocular melanomas
• Chordomas
• Chondrosarcomas

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

Intensity-modulated proton therapy (IMPT) for pediatric posterior fossa tumors can lead to high linear energy transfer (LET) values in the brainstem, especially when the tumor is located away from the brainstem, which raises concerns about potential biological dose increases.

Interestingly, when tumors invade or are closer to the brainstem, the biological dose (D × RBELET) is higher, indicating that treatment planning must consider tumor location to minimize risks to critical structures like the brainstem.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linear energy transfer distributions in the brainstem depending on tumour location in intensity-modulated proton therapy of paediatric cancer. Fjæra, LF., Li, Z., Ytre-Hauge, KS., et al.[2018]

A new optimization method for intensity modulated proton therapy (IMPT) effectively reduces high linear energy transfer (LET) in critical structures near tumor targets, enhancing treatment safety for patients with intracranial tumors.

In a study involving 5 patients with tumors overlapping sensitive areas like the brainstem and optic structures, the method successfully minimized high LET×D values while maintaining the physical dose distribution, potentially lowering the risk of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reoptimization of Intensity Modulated Proton Therapy Plans Based on Linear Energy Transfer. Unkelbach, J., Botas, P., Giantsoudi, D., et al.[2022]

In a study of 101 pediatric ependymoma patients, using a simultaneous integrated boost (SIB) with intensity-modulated proton therapy (IMPT) resulted in higher quality treatment indices and lower doses to organs at risk compared to standard radiation delivery methods.

The approach of dose escalation with SIB is feasible for certain patients, particularly those with supratentorial tumors, but caution is advised for infratentorial tumors due to potential risks to critical structures like the brainstem.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Dose Escalation in Patients With Intracranial Pediatric Ependymoma. Tensaouti, F., Ducassou, A., Chaltiel, L., et al.[2020]

The distal-edge avoidance-guided optimization method (DEAOpt) for intensity-modulated proton therapy (IMPT) effectively increases the biological effect in tumor areas while significantly reducing harmful effects in critical structures, such as the brainstem, compared to conventional dose-based optimization methods.

DEAOpt not only provides similar biological effects to LET-based optimization methods but also reduces computation time by over 30%, making it a more efficient approach for optimizing proton therapy treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A biological effect-guided optimization approach using beam distal-edge avoidance for intensity-modulated proton therapy. Bai, X., Lim, G., Grosshans, D., et al.[2021]

In a study of 17 pediatric patients treated with proton beam radiation for intracranial ependymoma, the median follow-up showed promising outcomes with local control at 86%, progression-free survival at 80%, and overall survival at 89%.

Proton therapy demonstrated significant advantages over intensity-modulated radiation therapy (IMRT) by providing similar tumor coverage while sparing more normal tissue, and intensity-modulated proton therapy (IMPT) may further enhance this sparing of critical structures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiotherapy for childhood ependymoma: initial clinical outcomes and dose comparisons. MacDonald, SM., Safai, S., Trofimov, A., et al.[2022]

Proton therapy (PT) for children with localized ependymoma showed high effectiveness, with a 3-year overall survival rate of 93.7% and a median total dose of 59.4 Gy, indicating it is a viable treatment option for this age group.

The study found that while PT was generally well tolerated, multiple tumor surgeries negatively impacted progression-free survival, and new severe late toxicities were observed in 11 patients, highlighting the need for careful treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of dose, volume, and outcome in children with localized, intracranial ependymoma treated with proton therapy within the prospective KiProReg Study. Peters, S., Merta, J., Schmidt, L., et al.[2022]

The novel intensity modulated proton arc therapy (IMPAT) method showed improved plan quality for ependymoma patients, achieving better dose homogeneity and conformity compared to traditional intensity-modulated proton therapy (IMPT) plans.

IMPAT plans resulted in higher relative biological effectiveness (RBE) enhancement, indicating a potential dosimetric benefit for tumors near critical organs, while maintaining similar maximum doses to the brainstem.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity modulated proton arc therapy via geometry-based energy selection for ependymoma. Cao, W., Li, Y., Zhang, X., et al.[2023]

The study explored a new method for optimizing intensity modulated proton therapy (IMPT) using linear energy transfer (LET) to improve treatment for 7 patients with head-and-neck and pancreatic cancers, showing significant variations in LET values that could impact treatment effectiveness.

By navigating between different treatment plans, the researchers found that accounting for LET could potentially improve the biological effectiveness of the treatment by up to 40%, suggesting a promising approach to enhance tumor targeting while protecting healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linear energy transfer-guided optimization in intensity modulated proton therapy: feasibility study and clinical potential. Giantsoudi, D., Grassberger, C., Craft, D., et al.[2022]

Using per-voxel constraints in intensity-modulated proton therapy (IMPT) significantly reduces harmful hot spots in the dose and linear energy transfer (LET) distribution, which can lead to brain necrosis in patients with base of skull cancer.

The LET-guided robust optimization method was shown to effectively minimize these hot spots compared to conventional dose-only optimization, resulting in lower xBD hot spots while maintaining comparable dose coverage for the target area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Per-voxel constraints to minimize hot spots in linear energy transfer-guided robust optimization for base of skull head and neck cancer patients in IMPT. Feng, H., Shan, J., Anderson, JD., et al.[2022]

The use of proton track-end objectives in intensity modulated proton therapy (IMPT) significantly reduced the linear energy transfer (LET) in critical structures by an average of 37%, while increasing LET in the target volume by 23%, without altering the physical dose distribution.

This method led to substantial reductions in the relative biological effectiveness (RBE)-weighted dose and normal tissue complication probabilities (NTCPs) by up to 19 percentage points, suggesting a safer and more effective approach to proton therapy that could be integrated into current clinical practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Introducing Proton Track-End Objectives in Intensity Modulated Proton Therapy Optimization to Reduce Linear Energy Transfer and Relative Biological Effectiveness in Critical Structures. Traneus, E., Ödén, J.[2019]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03750513

LET Optimized IMPT in Treating Pediatric Patients With ...

This phase I trial studies the side effects of linear energy transfer (LET) optimized image modulated proton therapy (IMPT) in treating pediatric patients with ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5815879/

Linear energy transfer incorporated intensity modulated ...

The purpose of this study was to investigate the feasibility of incorporating linear energy transfer (LET) into the optimization of intensity modulated proton ...

3.

connect.careboxhealth.com

connect.careboxhealth.com/en-US/trial/listing/254283

LET Optimized IMPT in Treating Pediatric Patients With ...

This phase I trial studies the side effects of linear energy transfer (LET) optimized image modulated proton therapy (IMPT) in treating ...

4.

withpower.com

withpower.com/trial/phase-1-ependymoma-3-2019-80bdc

Optimized Proton Therapy for Pediatric Ependymoma

This phase I trial studies the side effects of linear energy transfer (LET) optimized image modulated proton therapy (IMPT) in treating pediatric patients ...

5.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2018-02519

LET Optimized IMPT in Treating Pediatric Patients with ...

This phase I trial studies the side effects of linear energy transfer (LET) optimized image modulated proton therapy (IMPT) in treating pediatric patients ...

6.

clinicaltrial.be

clinicaltrial.be/en/details/66332?per_page=100&recruiting=1&enrolling_by_invitation=0&active_not_recruiting=0&not_yet_recruiting=0&completed=0&only_recruiting=1&only_eligible=0

LET Optimized IMPT in Treating Pediatric Patients With Ep...

I. To evaluate the safety of linear energy transfer (LET) optimized image modulated proton therapy (IMPT) (bio-IMPT) for pediatric patients with ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5450501/

Clinical evidence of variable proton biological ...

We analyzed pediatric ependymoma patients who received proton therapy to determine if areas of normal tissue damage indicated by post-treatment ...