Proton Therapy for Brain Tumors

(HiPPI Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Emory University

Disqualifiers: Pregnancy, Prior overlapping radiation, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3.5-4 weeks

70 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Proton Therapy for Brain Tumors?

Research shows that hypofractionated proton therapy, which is a type of radiation treatment, has been safely used and is effective for treating certain types of lung and prostate cancers. This suggests it might also be effective for brain tumors, as it allows for precise targeting of the tumor while minimizing damage to surrounding healthy tissue. ^{1 2 3 4 5}

Is proton therapy generally safe for humans?

Research shows that proton therapy, including hypofractionated versions, is generally safe for treating various cancers like prostate, lung, and head-and-neck, with studies reporting manageable side effects. ^{6 7 8 9 10}

How is proton therapy for brain tumors different from other treatments?

Proton therapy for brain tumors is unique because it delivers radiation with a steep dose gradient, minimizing damage to surrounding healthy tissues compared to traditional photon therapy. This makes it particularly beneficial for tumors in complex areas or near sensitive tissues, reducing potential side effects. ^{3 11 12 13 14}

What is the purpose of this trial?

This trial studies how well a new form of radiation therapy works for patients with certain types of brain tumors. The goal is to see if this method can effectively control tumor growth while reducing side effects and making treatment more convenient.

Research Team

Bree R. Eaton, MD

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Eligibility Criteria

This trial is for individuals with benign brain tumors, including meningiomas, pituitary adenomas, and schwannomas. Participants must consent to treatment and be recommended for proton or photon radiation therapy. Pregnant women can't join, and women who can have children must test negative for pregnancy and agree to use effective birth control.

Inclusion Criteria

I am advised to undergo a specific type of radiation therapy.

I have a diagnosed benign brain or nerve sheath tumor, including specific types like meningiomas.

Signed informed consent

Exclusion Criteria

Pregnant females are excluded

I am a woman who can have children and have a negative pregnancy test.

I have had radiation therapy in the same area where I need treatment now.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo hypofractionated proton or photon radiation therapy daily, Monday-Friday over 17-20 fractions for 3.5-4 weeks

3.5-4 weeks

Daily visits, Monday-Friday

Follow-up

Participants are monitored for safety, effectiveness, and local tumor control after treatment

Up to 3 years

Treatment Details

Interventions

• Hypofractionated Radiation Therapy
• Photon Beam Radiation Therapy
• Proton Beam Radiation Therapy

Trial Overview The HiPPI Study is testing if hypofractionated proton or photon radiation therapy is effective in treating benign brain tumors by delivering higher doses over a shorter period. The goal is to see if this approach kills more tumor cells while reducing side effects and costs.

Participant Groups

Group I: Cohort II (hypofractionated radiation therapy) Experimental Treatment 5 Interventions

Patients with pathologically confirmed World Health Organization (WHO) grade 2-3 meningiomas undergo hypofractionated proton or photon radiation therapy daily, Monday-Friday over 20 fractions for 3.5-4 weeks in the absence of disease progression or unacceptable toxicity.

Group II: Cohort I (hypofractionated radiation therapy) Experimental Treatment 5 Interventions

Patients with benign and radiographically diagnosed intracranial tumors undergo hypofractionated proton or photon radiation therapy daily, Monday-Friday over 17 fractions for 3.5-4 weeks in the absence of disease progression or unacceptable toxicity.

Hypofractionated Radiation Therapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Approved in European Union as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Approved in Canada as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Hypofractionated proton therapy (PT) for breast cancer, particularly in accelerated partial breast irradiation (APBI), shows a favorable dosimetric profile compared to traditional photon-based techniques, suggesting potential benefits in targeting tumors while sparing healthy tissue.

Current evidence is limited to APBI applications, and while dosimetric advantages are noted, more long-term studies are needed to confirm whether these benefits lead to improved clinical outcomes and reduced long-term toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated proton therapy in breast cancer: where are we? A critical review of the literature. Alterio, D., La Rocca, E., Volpe, S., et al.[2022]

In a phase 1/2 trial involving 28 patients with locally advanced non-small cell lung cancer (NSCLC), hypofractionated proton therapy combined with chemotherapy resulted in impressive 1-year overall survival rates of 89%, significantly higher than the 62% benchmark from previous studies.

The treatment was well-tolerated, with no severe esophagitis and only 14% of patients experiencing significant radiation-related pulmonary toxicity, suggesting that proton therapy may offer a safer alternative for patients with advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiation with Hypofractionated Proton Therapy in Stage II-III Non-Small Cell Lung Cancer: A Proton Collaborative Group Phase 2 Trial. Hoppe, BS., Nichols, RC., Flampouri, S., et al.[2022]

In a study involving 200 patients with early-stage prostate cancer, extreme hypofractionated proton therapy (36.25 GyE in five fractions) demonstrated feasibility with a low rate of acute toxicity, where no patients experienced severe (G3) side effects.

After a median follow-up of 36 months, the treatment showed promising effectiveness, with no local recurrences of cancer and a low PSA relapse rate of 1.08% in low-risk and 6.5% in intermediate-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extreme hypofractionated proton radiotherapy for prostate cancer using pencil beam scanning: Dosimetry, acute toxicity and preliminary results. Kubeš, J., Vondráček, V., Andrlik, M., et al.[2020]

In a study of 111 patients with early-stage lung cancer, hypofractionated proton beam therapy showed improved overall survival rates with higher doses, achieving a 4-year overall survival of 51% at the 70 Gy dose level.

The treatment was well-tolerated, with no significant complications from radiation pneumonitis, and pulmonary function remained stable one year after therapy, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose hypofractionated proton beam radiation therapy is safe and effective for central and peripheral early-stage non-small cell lung cancer: results of a 12-year experience at Loma Linda University Medical Center. Bush, DA., Cheek, G., Zaheer, S., et al.[2018]

Hypofractionated radiation therapy (HypoRT) was found to be effective in treating inoperable advanced non-small cell lung cancer (NSCLC), with an overall response rate of 83% among 30 patients, and a median follow-up of 13 months.

The treatment was well-tolerated, with manageable acute toxicities; however, 37% of patients experienced locoregional recurrence, and 57% developed distant metastasis, indicating the need for further studies to compare HypoRT with conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer. Osti, MF., Agolli, L., Valeriani, M., et al.[2018]

In a study of 289 prostate cancer patients, hypofractionated proton beam therapy (PBT) showed no significant differences in acute adverse event rates or quality of life, as measured by the International Prostate Symptom Score (IPSS), compared to conventionally fractionated PBT.

The study evaluated patients treated with different doses (2.0, 2.5, and 3.0 Gy RBE per fraction) and found that factors like diabetes, age, and androgen deprivation therapy did not influence the IPSS outcomes, suggesting that hypofractionated PBT is a safe option without increased toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity and patient-reported symptom score after conventional versus moderately hypofractionated proton therapy for prostate cancer. Iizumi, T., Ishikawa, H., Sekino, Y., et al.[2022]

In a study of 20 patients with central lung cancer treated with high total dose hypofractionated proton beam therapy, there were no severe toxicities (Grade 3 or higher), indicating a strong safety profile for this treatment approach.

The therapy resulted in a 2-year overall survival rate of 73.8% and a local control rate of 78.5%, demonstrating its efficacy, especially in operable patients who had a 100% survival rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Dose Hypofractionated Proton Beam Therapy is a Safe and Feasible Treatment for Central Lung Cancer. Ono, T., Yabuuchi, T., Nakamura, T., et al.[2019]

The phase 1 trial involving 18 patients with stage II or III non-small cell lung cancer demonstrated that hypofractionated proton therapy combined with chemotherapy has an acceptable safety profile, with no severe adverse events attributed to radiation therapy.

The study did not identify a maximum tolerated dose, and while two severe adverse events occurred, they were linked to chemotherapy rather than the proton therapy, suggesting that this treatment approach is safe for further investigation in phase 2 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated Proton Therapy with Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Trial from the University of Florida and Proton Collaborative Group. Hoppe, BS., Nichols, RC., Flampouri, S., et al.[2021]

High-dose, hypofractionated radiotherapy (HFRT) demonstrated a high overall response rate of 79% and a one-year local-progression free rate of 50% in treating head-and-neck malignancies, based on a retrospective analysis of 48 patients.

The study found that delivering doses of 6Gray or higher per fraction improved locoregional control, and increased toxicity was not observed with doses of 8Gray or more, suggesting that HFRT can be both effective and safe for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose hypofractionated radiotherapy is effective and safe for tumors in the head-and-neck. Teckie, S., Lok, BH., Rao, S., et al.[2022]

In a study of 56 breast cancer patients receiving hypofractionated external beam radiotherapy (HFRT) after mastectomy, the treatment was well tolerated with mild to moderate acute skin toxicity, and no severe hematological toxicity was observed, indicating a favorable safety profile.

HFRT effectively delivered targeted doses to the chest wall while minimizing exposure to surrounding organs, with mean lung and heart doses remaining within safe limits, suggesting that HFRT can be a viable option for post-mastectomy radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Study on Dosimetric Outcomes and Acute Toxicity of Post Mastectomy Adjuvant Hypofractionated Radiotherapy for Breast Cancer. Deshmukh, S., Sharan, K., Fernandes, DJ., et al.[2022]

Proton therapy significantly reduces the integral dose to patients, with approximately 60% lower exposure compared to photon therapies, making it particularly beneficial for pediatric patients with developing tissues.

While proton therapy shows promising results and safety for various tumors, its higher cost compared to photon therapy raises questions about cost-effectiveness, especially for adult cancers like prostate cancer, necessitating further comparative studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton therapy in the clinic. DeLaney, TF.[2022]

Proton therapy offers steeper dose gradients and better dose conformality than photon therapy, making it particularly effective for treating skull base tumors that require higher doses for effective control.

This review highlights the potential of proton therapy to reduce radiation-related side effects in brain tumors, suggesting it may be a safer option for patients compared to traditional photon therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protons vs Photons for Brain and Skull Base Tumors. Ahmed, SK., Brown, PD., Foote, RL.[2022]

Proton beam therapy (PBT) is feasible for treating infants with central nervous system tumors, showing promising short-term outcomes with a 3-year overall survival rate of 76.5% among 51 infants studied.

However, the treatment is associated with significant logistical challenges and potential for higher-grade toxicities, including late effects like endocrinopathy and hearing loss, highlighting the need for careful monitoring and longer follow-up to assess long-term impacts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Proton Beam Therapy for Infants with Brain Tumours: Experiences from the Prospective KiProReg Registry Study. Jazmati, D., Steinmeier, T., Ahamd Khalil, D., et al.[2021]

Proton beam therapy (PBT) usage in the US increased from 0.4% in 2004 to 1.2% in 2018, particularly among patients with cancers recommended for PBT by the American Society of Radiation Oncology, indicating growing acceptance and application of this treatment.

While PBT use for prostate cancer temporarily decreased from 2011 to 2014, it rebounded by 2018, suggesting fluctuations in treatment preferences or insurance coverage that may influence patient access to this advanced therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Proton Beam Therapy Use Among Patients With Newly Diagnosed Cancer in the US, 2004-2018. Nogueira, LM., Jemal, A., Yabroff, KR., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Hypofractionated proton therapy in breast cancer: where are we? A critical review of the literature. [2022]

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

Chemoradiation with Hypofractionated Proton Therapy in Stage II-III Non-Small Cell Lung Cancer: A Proton Collaborative Group Phase 2 Trial. [2022]

3. Australia pubmed.ncbi.nlm.nih.gov

Extreme hypofractionated proton radiotherapy for prostate cancer using pencil beam scanning: Dosimetry, acute toxicity and preliminary results. [2020]

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

High-dose hypofractionated proton beam radiation therapy is safe and effective for central and peripheral early-stage non-small cell lung cancer: results of a 12-year experience at Loma Linda University Medical Center. [2018]

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

Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer. [2018]

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

Acute toxicity and patient-reported symptom score after conventional versus moderately hypofractionated proton therapy for prostate cancer. [2022]

7. Poland pubmed.ncbi.nlm.nih.gov

High Dose Hypofractionated Proton Beam Therapy is a Safe and Feasible Treatment for Central Lung Cancer. [2019]

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

Hypofractionated Proton Therapy with Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Trial from the University of Florida and Proton Collaborative Group. [2021]

9. England pubmed.ncbi.nlm.nih.gov

High-dose hypofractionated radiotherapy is effective and safe for tumors in the head-and-neck. [2022]

10. India pubmed.ncbi.nlm.nih.gov

A Study on Dosimetric Outcomes and Acute Toxicity of Post Mastectomy Adjuvant Hypofractionated Radiotherapy for Breast Cancer. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Proton therapy in the clinic. [2022]

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

Protons vs Photons for Brain and Skull Base Tumors. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Feasibility of Proton Beam Therapy for Infants with Brain Tumours: Experiences from the Prospective KiProReg Registry Study. [2021]

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

Assessment of Proton Beam Therapy Use Among Patients With Newly Diagnosed Cancer in the US, 2004-2018. [2022]