Proton Beam vs IMRT for Brain Cancer

Not currently recruiting at 36 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NRG Oncology

Must not be taking: Memantine

Disqualifiers: Metastatic disease, Prior malignancy, Prior cranial radiotherapy, Prior chemotherapy, Neurologic or psychiatric disease, others

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

Compensation: Varies

Number of Visits: 30

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two types of radiation therapy—proton beam and intensity-modulated radiation therapy (IMRT)—to determine which better preserves brain function in patients with IDH mutant grade II or III gliomas. Proton beam therapy targets the tumor with tiny charged particles, while IMRT uses x-ray beams, both aiming to minimize damage to healthy brain tissue. The trial seeks participants diagnosed with these specific gliomas who have undergone surgery and can have MRI scans. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in brain cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, the use of memantine during or after radiation is not allowed, and only adjuvant temozolomide therapy will be used during the trial.

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

Research has shown that proton beam radiation therapy is generally safe for treating brain tumors. One study found a low rate of serious side effects, such as brainstem damage, in children who received this treatment. Another study demonstrated that proton therapy controlled tumors as effectively as traditional radiation but with fewer harmful side effects.

For intensity-modulated radiation therapy (IMRT), research indicates it is well-tolerated, with patients experiencing fewer side effects compared to older radiation methods. Both proton therapy and IMRT precisely target the tumor, helping to protect healthy brain tissue from damage.

In this trial, both treatments are combined with temozolomide, a common chemotherapy drug. Researchers will closely monitor participants to ensure safety and manage any side effects that might occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for brain cancer because they offer two advanced forms of radiation therapy that might reduce side effects while maintaining effectiveness. Proton beam radiation therapy is distinctive because it delivers radiation more precisely, potentially sparing healthy brain tissue and reducing long-term side effects. Intensity-Modulated Radiation Therapy (IMRT), a more established method, also aims for precision by modulating the radiation intensity, but proton therapy may offer even greater accuracy. By comparing these treatments, researchers hope to determine if proton therapy provides a safer, yet equally effective, alternative to the standard IMRT.

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

This trial compares proton beam radiation therapy with intensity-modulated radiation therapy (IMRT) for treating brain cancer. Studies have shown that proton beam radiation therapy can precisely target brain tumors, causing less harm to normal brain tissue. This precision may help maintain brain function better than other radiation types, reducing the risk of mental decline. Proton therapy has also effectively controlled brain tumors, potentially with fewer side effects. In contrast, IMRT uses x-ray beams shaped to fit the tumor, aiming to protect healthy tissues. Both treatments in this trial aim to treat glioma effectively, but proton therapy might better preserve quality of life. ^{5 6 7 8 9}

Who Is on the Research Team?

David R Grosshans

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for English-speaking adults with a specific brain tumor (IDH mutant grade II or III glioma). They must be in good physical condition, have certain blood counts and organ functions within normal ranges, and have had recent MR imaging. Patients who've had prior brain radiation, severe psychiatric diseases affecting cognition, or are severely immunocompromised can't participate.

Inclusion Criteria

I speak English and can complete assessments in it.

I must have a detailed MRI with contrast for my treatment planning.

I have financial approval for proton therapy before the next treatment phase.

Exclusion Criteria

My cancer is not located in the lower part of my brain.

I am not using memantine during or after radiation treatment.

I was hospitalized for heart failure that is moderately severe or worse in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Patients undergo either photon-based IMRT or proton beam radiation therapy once daily, 5 days a week for 6 weeks for a total of 30 fractions.

6 weeks

30 visits (in-person)

Chemotherapy

Beginning 28 days after completion of radiation therapy, patients receive standard of care temozolomide for 5 days. Treatment repeats every 28 days for up to 12 courses.

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups at 6 and 12 months, and then yearly for 10 years.

10 years

Annual visits

What Are the Treatments Tested in This Trial?

Interventions

• IMRT (Intensity-Modulated Radiation Therapy)
• Proton Beam Radiation Therapy
• Temozolomide

Trial Overview

The study compares two types of advanced radiation therapy: Proton Beam Radiation Therapy and Intensity-Modulated Radiation Therapy (IMRT), along with Temozolomide chemotherapy. It aims to see which method better preserves brain function while treating the tumor effectively.

How Is the Trial Designed?

Group I: Arm II (proton beam radiation therapy, temozolomide) Experimental Treatment 7 Interventions

Patients undergo proton beam radiation therapy QD, 5 days a week for 6 weeks for a total of 30 fractions. Beginning 28 days after completion of radiation therapy, patients receive standard of care temozolomide for 5 days. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression of unacceptable toxicity. Patients undergo MRI and collection of blood samples throughout the trial.

Group II: Arm I (photon-based IMRT, temozolomide) Active Control 7 Interventions

Patients undergo photon-based IMRT QD, 5 days a week for 6 weeks for a total of 30 fractions. Beginning 28 days after completion of radiation therapy, patients receive standard of care temozolomide for 5 days. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression of unacceptable toxicity. Patients undergo MRI and collection of blood samples throughout the trial.

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 involving 394 patients with localized prostate cancer, proton beam therapy (PBT) showed lower dosimetry for bladder and rectum compared to intensity-modulated radiation therapy (IMRT), suggesting a potential for reduced exposure to surrounding tissues.

However, after matching patients on risk factors and adjusting for confounders, there were no significant differences in the rates of acute or late gastrointestinal and genitourinary toxicities between PBT and IMRT, indicating similar safety profiles for both treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case-matched study of toxicity outcomes after proton therapy and intensity-modulated radiation therapy for prostate cancer. Fang, P., Mick, R., Deville, C., et al.[2022]

Proton beam radiation therapy (PBRT) significantly spares normal tissues compared to intensity-modulated radiation therapy (IMRT), as shown by lower radiation doses to critical structures like the brainstem and spinal cord in a study of 41 patients with head and neck cancers.

Patients receiving PBRT experienced significantly lower rates of acute treatment-related toxicities, including dysgeusia, mucositis, and nausea, indicating that PBRT may be a safer option for treating ipsilateral head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam radiation therapy results in significantly reduced toxicity compared with intensity-modulated radiation therapy for head and neck tumors that require ipsilateral radiation. Romesser, PB., Cahlon, O., Scher, E., 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]

Proton therapy (IMPT) provides better dose distribution and sparing of healthy tissues compared to photon therapy (IMRT) for pediatric patients with intracranial tumors, particularly benefiting younger patients with supratentorial tumors.

Infratentorial tumors showed significant sparing of the optic chiasm with IMPT, while brainstem sparing was less pronounced, indicating that IMPT can effectively reduce radiation exposure to critical structures in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Target Location, Size, and Patient Age on Normal Tissue Sparing- Proton and Photon Therapy in Paediatric Brain Tumour Patient-Specific Approach. Dell'Oro, M., Short, M., Wilson, P., et al.[2020]

Intensity-modulated photon radiotherapy (IMRT) provided better dose conformity to the prostate cancer target compared to three-dimensional conformal proton therapy (3D-CPT), while both methods effectively delivered the prescribed dose to at least 98% of the target volume.

Proton therapy, particularly with optimized configurations, significantly reduced radiation exposure to the bladder and rectum at lower doses, indicating a potential advantage in sparing healthy tissues during prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy treatment of early-stage prostate cancer with IMRT and protons: a treatment planning comparison. Trofimov, A., Nguyen, PL., Coen, JJ., et al.[2020]

Proton beam therapy (PBT) for prostate cancer patients receiving pelvic radiation significantly reduces acute gastrointestinal (GI) toxicity compared to intensity modulated radiation therapy (IMXT), with rates of grade 1, 2, and 3 GI toxicity at 16.4%, 2.4%, and 0%, respectively.

The study involved 85 patients with a median follow-up of 14.5 months, and while GU toxicity was higher, the results suggest that PBT may spare the small bowel, leading to less GI side effects, warranting further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimal toxicity after proton beam therapy for prostate and pelvic nodal irradiation: results from the proton collaborative group REG001-09 trial. Chuong, MD., Hartsell, W., Larson, G., et al.[2018]

The study compared intensity-modulated radiotherapy (IMRT) using the Peacock system with stereotactically guided conformal radiotherapy (SCRT) in five patients with medium-sized convex-shaped brain tumors, finding that IMRT provided slightly better planning target volume (PTV) coverage.

While the doses to organs at risk (OAR) were higher with the Peacock method, all doses remained below clinically acceptable thresholds, indicating that IMRT can be a safe option for treating these tumors, though further improvements in planning methods may enhance outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of intensity-modulated tomotherapy with stereotactically guided conformal radiotherapy for brain tumors. Khoo, VS., Oldham, M., Adams, EJ., et al.[2019]

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This study revealed a low incidence of symptomatic brainstem toxicity and related mortality among pediatric brain tumor patients undergoing proton beam ...

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advances.massgeneral.org

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Tracking Outcomes in Proton Therapy for Cancer

Massachusetts General Hospital clinician-researchers work to define which patients can benefit most from advanced proton therapy for cancer.

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pmc.ncbi.nlm.nih.gov

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PBT demonstrated equivalent tumor control and survival outcomes compared to conventional therapies while offering significantly reduced risks of ...

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Is Proton Therapy Safer than Traditional Radiation? - NCI

After 3 years, 46% of patients in the proton therapy group and 49% of those in the traditional radiation therapy group were cancer free. Fifty- ...