Proton Beam vs IMRT for Brain Cancer

Recruiting at 35 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

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This randomized phase II clinical trial studies the side effects and how well proton beam or intensity-modulated radiation therapy works in preserving brain function in patients with IDH mutant grade II or III glioma. Proton beam radiation therapy uses tiny charged particles to deliver radiation directly to the tumor and may cause less damage to normal tissue. Intensity-modulated or photon beam radiation therapy uses high-energy x-ray beams shaped to treat the tumor and may also cause less damage to normal tissue. It is not yet known if proton beam radiation therapy is more effective than photon-based beam intensity-modulated radiation therapy in treating patients with glioma.

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 proton beam therapy safe for brain cancer patients?

Proton beam therapy is generally considered safe and can reduce side effects compared to traditional radiation therapy, as it delivers more precise doses to the target area, sparing normal tissues. This has been observed in studies for both brain and prostate cancers, suggesting a potential safety advantage over other forms of radiation therapy. ^{1 2 3 4 5}

How does Proton Beam Radiation Therapy differ from IMRT for brain cancer treatment?

Proton Beam Radiation Therapy is unique because it can deliver radiation more precisely to the tumor, sparing more of the surrounding healthy tissue compared to Intensity-Modulated Radiation Therapy (IMRT). This precision can lead to fewer side effects, making it a potentially better option for treating brain cancer. ^{2 6 7 8 9}

What data supports the effectiveness of the treatment Proton Beam vs IMRT for Brain Cancer?

Research shows that proton therapy can reduce radiation exposure to healthy tissues compared to traditional methods like IMRT, which may lead to fewer side effects and maintain good treatment outcomes, as seen in studies on head and neck tumors and pediatric brain tumors. ^{2 6 7 10 11}

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

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]

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]

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]

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]

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]

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]

Citations

1. 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]

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

Advantage of protons compared to conventional X-ray or IMRT in the treatment of a pediatric patient with medulloblastoma. [2022]

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]

4. Ireland 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. [2022]

5. Switzerland 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. [2020]

6. England 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. [2018]

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

Comparison of intensity-modulated tomotherapy with stereotactically guided conformal radiotherapy for brain tumors. [2019]

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

A case-matched study of toxicity outcomes after proton therapy and intensity-modulated radiation therapy for prostate cancer. [2022]

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

Finding Value for Protons: The Case of Prostate Cancer? [2018]

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

Differential dosimetric benefit of proton beam therapy over intensity modulated radiotherapy for a variety of targets in patients with intracranial germ cell tumors. [2022]

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

Radiotherapy treatment of early-stage prostate cancer with IMRT and protons: a treatment planning comparison. [2020]