Pulsed Radiotherapy for Brain Cancer

Overseen by Jiayi Huang, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Washington University School of Medicine

Must not be taking: Bevacizumab, Anti-VEGF

Disqualifiers: Leptomeningeal, Metastatic, Radiation necrosis, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial studies the side effects of a new method of giving radiation in small, timed doses, in patients with certain types of brain tumors who have had earlier treatments. This approach may be more effective and less harmful.

Will I have to stop taking my current medications?

The trial requires you to stop taking bevacizumab (a medication used to treat certain types of cancer) at least 4 weeks before starting the study. Other medications like chemotherapy or immunotherapy can be continued, but it's best to discuss with your doctor.

What data supports the effectiveness of the treatment TMPRT for brain cancer?

Research shows that pulsed radiation therapy (PRT) can effectively control tumors and protect normal tissue better than standard radiotherapy in brain cancer models. Additionally, combining pulsed radiation with drugs like temozolomide has shown promising results in treating resistant brain tumors in animal studies. ^{1 2 3 4 5}

Is pulsed radiotherapy generally safe for humans?

There is limited safety data specifically on pulsed radiotherapy for brain cancer in humans, but related treatments like temozolomide with radiation therapy have shown some side effects such as fatigue, nausea, and blood-related issues. Severe side effects are rare, but they can include significant blood problems. ^{3 5 6 7 8}

How is the treatment TMPRT different from other treatments for brain cancer?

TMPRT (Temporally-modulated Pulsed Radiation Therapy) is unique because it delivers radiation in pulses, which has shown to effectively control tumors while better sparing normal tissue compared to standard radiotherapy. This approach is being investigated for its potential benefits in treating newly diagnosed glioblastoma, a type of aggressive brain cancer. ^{1 2 9 10 11}

Research Team

Jiayi Huang, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults with IDH-mutant gliomas (brain tumors) who've had prior radiation. They should have a life expectancy of over a year, be able to consent, and women must use birth control. It's not for pregnant individuals or those with certain medical conditions that conflict with the treatment.

Inclusion Criteria

I had targeted radiation to the same area before, but the total dose was under 75 Gy and it was over 6 months ago.

I am using or willing to use birth control during the study.

I had external beam radiation therapy over 2 years ago.

Exclusion Criteria

You are currently pregnant.

I am not using bevacizumab or similar drugs for my treatment.

My cancer has spread to the lining of my brain or other parts of my body.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive temporally-modulated pulsed radiation therapy (TMPRT) daily as 10 pulses of 0.2 Gy each with a 3-minute interval between pulses to a total dose of 54 Gy at 2 Gy per day. Treatment continues for a total of 27 fractions.

6 weeks

Daily visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of quality of life and symptom burden.

12 months

Assessments at 3, 6, and 12 months

Treatment Details

Interventions

• TMPRT (Radiation Therapy)

Trial Overview The study tests TMPRT, a type of radiotherapy given in small doses at set intervals to potentially increase effectiveness and reduce side effects compared to one large dose. The focus is on patients who've previously received brain radiation therapy.

Participant Groups

Group I: Arm 1: temporally-modulated pulsed radiotherapy (TMPRT) Experimental Treatment 1 Intervention

Patients receive TMPRT daily as 10 pulses of 0.2 Gy each with a 3-minute interval between pulses (effective dose rate = 0.0667 Gy/min) to a total dose of 54 Gy at 2 Gy per day. Treatment continues for a total of 27 fractions in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

David H. Perlmutter

Washington University School of Medicine

Chief Executive Officer since 2015

MD from Washington University School of Medicine

Paul Scheel

Washington University School of Medicine

Chief Medical Officer since 2022

MD from Washington University School of Medicine

Findings from Research

In a prospective study of 20 patients with newly diagnosed glioblastoma, pulsed radiation therapy (PRT) combined with temozolomide showed promising effectiveness, with a median overall survival of 20.9 months, which is significantly longer than the 14 months observed in a matched cohort receiving standard radiotherapy.

PRT treatment maintained neurocognitive function and quality of life over the 21-month follow-up period, indicating that this therapy is not only effective but also safe for patients' cognitive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed radiation therapy for the treatment of newly diagnosed glioblastoma. Almahariq, MF., Quinn, TJ., Arden, JD., et al.[2021]

A shortened course of radiotherapy (51 Gy in 17 fractions) for malignant glioma patients showed similar survival outcomes to more aggressive treatments, with median survival times ranging from 5 to 68 months based on prognostic groupings.

The treatment was associated with low toxicity and acceptable acute side effects, making it a viable option for patients in poorer prognostic groups (RTOG groups 4-6), but not recommended for those with better long-term survival prospects (RTOG groups 1-3) due to a lack of long-term neurocognitive data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short course radiotherapy is an appropriate option for most malignant glioma patients. Kleinberg, L., Slick, T., Enger, C., et al.[2019]

Pulsed low-dose radiation therapy (PLRT) combined with temozolomide (TMZ) significantly delayed tumor growth in a murine model of radioresistant glioblastoma multiforme (GBM), showing superior efficacy compared to standard radiation therapy with TMZ.

PLRT+TMZ resulted in less damage to normal brain tissue and increased vascularization, suggesting it may be a safer and more effective treatment option for GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed versus conventional radiation therapy in combination with temozolomide in a murine orthotopic model of glioblastoma multiforme. Lee, DY., Chunta, JL., Park, SS., et al.[2022]

In a study using a head and neck cancer model with 30 mice, low-dose pulsed radiation treatment (PRT) combined with cisplatin (CDDP) significantly delayed tumor growth more than standard radiation therapy (SRT) combined with CDDP, with PRT achieving an average growth delay of 80.2 days compared to 62.3 days for SRT.

PRT also preserved the tumor's vascular network better than SRT, as indicated by differences in tumor vessel density, which may contribute to its enhanced efficacy in combination with CDDP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed Radiation Therapy With Concurrent Cisplatin Results in Superior Tumor Growth Delay in a Head and Neck Squamous Cell Carcinoma Murine Model. Meyer, K., Krueger, SA., Kane, JL., et al.[2022]

In a study of 9 patients with brain metastases from lung adenocarcinoma, the combination of intensity-modulated radiation therapy (IMRT) and temozolomide (TMZ) resulted in a high objective response rate of 77.8%, with one complete response and six partial responses, confirming the efficacy of this treatment approach.

Patients receiving the combination treatment experienced fewer severe adverse effects compared to those who only received IMRT, with no grade ≥3 hematologic toxicities reported, and an improvement in quality of life was noted, indicating that the addition of TMZ is both effective and relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy combined with concomitant temozolomide for brain metastases from lung adenocarcinoma. Li, J., Chai, X., Cao, Y., et al.[2020]

In a study of 87 newly diagnosed glioblastoma patients, only 5% experienced severe myelotoxicity during treatment with temozolomide (TMZ) and radiation therapy, indicating that while the risk exists, it is relatively low.

Factors such as female sex, low pretreatment platelet counts, and specific genetic markers were identified as potential predictors of severe myelotoxicity, suggesting that personalized treatment approaches could help mitigate risks in vulnerable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study. Lombardi, G., Rumiato, E., Bertorelle, R., et al.[2018]

In a study of 260 patients treated for brain and skull base tumors with photon and particle therapies, no unexpected severe toxicities were reported, indicating a favorable safety profile for these treatments.

The use of particle therapy, particularly protons and carbon ions, shows promise in potentially reducing the risk of secondary malignancies and improving neurocognitive outcomes, although longer follow-up is needed to confirm these benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base. Combs, SE., Kessel, K., Habermehl, D., et al.[2016]

Temozolomide (TMZ) is generally safe with mild to moderate side effects, but this case report highlights a rare instance of severe aplastic anemia (AA) in a 68-year-old female patient following treatment for glioblastoma, indicating a potential serious risk associated with the drug.

The patient's AA was managed successfully with supportive care, including platelet transfusions and growth factor treatment, and her blood counts returned to normal within 38 days, emphasizing the importance of monitoring blood parameters during and after TMZ treatment to detect such rare toxicities early.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. Gilbar, PJ., Pokharel, K., Mangos, HM.[2022]

Proton therapy (PT) offers a promising alternative to traditional photon-based radiotherapy for glioblastoma multiforme (GBM) patients by potentially reducing off-target irradiation and associated toxicities, which is crucial given the aggressive nature of this tumor.

Current research suggests that PT may enhance treatment outcomes for glioma patients, particularly in terms of cognitive sparing and the feasibility of high-rate 'FLASH' radiotherapy, highlighting the need for ongoing clinical trials to further evaluate its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiotherapy for glioma and glioblastoma. Goff, KM., Zheng, C., Alonso-Basanta, M.[2023]

In a study of 24 high-grade glioma patients, significant volumetric changes in the tumor bed were observed between immediate postoperative MRI and MRI taken before radiation therapy, leading to a decrease in the volume of brain tissue treated with 46 Gy of radiation.

Using delayed MRI for radiation treatment planning can reduce the volume of healthy brain tissue exposed to radiation, potentially minimizing side effects, while still maintaining effective local control of the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating changes in radiation treatment volumes from post-operative to same-day planning MRI in High-grade gliomas. Champ, CE., Siglin, J., Mishra, MV., et al.[2021]

Low-dose pulsed radiation therapy (PRT) and standard radiation therapy (SRT) both effectively delayed tumor growth in head and neck squamous cell carcinoma xenografts, indicating that PRT can be a viable alternative to SRT.

PRT resulted in lower levels of tumor hypoxia compared to SRT in radiosensitive UT-SCC-14 tumors, suggesting that PRT may improve treatment outcomes by reducing hypoxic conditions that can limit the effectiveness of radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Pulsed Radiation Therapy on Tumor Oxygenation in 2 Murine Models of Head and Neck Squamous Cell Carcinoma. Wobb, J., Krueger, SA., Kane, JL., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Pulsed radiation therapy for the treatment of newly diagnosed glioblastoma. [2021]

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

Short course radiotherapy is an appropriate option for most malignant glioma patients. [2019]

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

Pulsed versus conventional radiation therapy in combination with temozolomide in a murine orthotopic model of glioblastoma multiforme. [2022]

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

Pulsed Radiation Therapy With Concurrent Cisplatin Results in Superior Tumor Growth Delay in a Head and Neck Squamous Cell Carcinoma Murine Model. [2022]

5. Greece pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy combined with concomitant temozolomide for brain metastases from lung adenocarcinoma. [2020]

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

Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base. [2016]

8. England pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. [2022]

9. China pubmed.ncbi.nlm.nih.gov

Proton radiotherapy for glioma and glioblastoma. [2023]

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

Evaluating changes in radiation treatment volumes from post-operative to same-day planning MRI in High-grade gliomas. [2021]

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

The Effects of Pulsed Radiation Therapy on Tumor Oxygenation in 2 Murine Models of Head and Neck Squamous Cell Carcinoma. [2022]