Accelerated Radiation Therapy for Glioblastoma

Recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Carbidopa/levodopa

Disqualifiers: Pregnancy, Nursing, IDH mutation, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1-6 weeks

170 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are taking carbidopa/levodopa, you must stop at least 48 hours before an 18F-DOPA-PET scan.

What data supports the effectiveness of Accelerated Hypofractionated Radiation Therapy for glioblastoma?

Research shows that hypofractionated radiation therapy, which involves giving larger doses of radiation over a shorter period, can be effective for glioblastoma, especially in elderly or frail patients. It has been found to be as effective as traditional longer courses of radiation, with the added benefit of a shorter treatment time. ^{1 2 3 4 5}

Is accelerated radiation therapy safe for humans?

Accelerated radiation therapy, also known as hypofractionated radiation therapy, has been found to be a safe treatment option for glioblastoma patients, including those who are elderly or have other health challenges. While there is a risk of increased toxicity in some cases, studies have shown that most patients tolerate the treatment well, and it is considered a feasible option. ^{1 4 6 7 8}

How is Accelerated Hypofractionated Radiation Therapy different from other treatments for glioblastoma?

Accelerated Hypofractionated Radiation Therapy is unique because it delivers higher doses of radiation over a shorter period, which can be more convenient for patients and may reduce treatment time without compromising effectiveness or increasing side effects compared to standard radiation therapy. ^{1 2 3 4 9}

What is the purpose of this trial?

This phase II trial compares the effect of short course radiotherapy (RT) to standard course RT for the treatment of patients diagnosed with glioblastoma (GBM). The researchers want to learn whether the shorter course treatment is non-inferior (not worse than the standard of care), for patients with GBM. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Short course radiotherapy delivers higher doses of radiation over a shorter period of time and may kill more tumor cells and have fewer side effects.

Research Team

Roman O. Kowalchuk, MD

Principal Investigator

Mayo Clinic in Rochester

William G. Breen, M.D.

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

This trial is for adults over 18 with confirmed glioblastoma, able to complete questionnaires and have an ECOG performance status of 3 or less. Participants must consent in writing, be willing to follow up at the enrolling institution, and have a postoperative tumor size ≤6 cm. Excluded are those with IDH mutation tumors, MRI/18F-DOPA-PET scan issues, certain medication use, not receiving radiation at specified locations, or unwilling to use contraception.

Inclusion Criteria

Ability to complete questionnaire(s) by themselves or with assistance

Provide written informed consent

My diagnosis of glioblastoma has been confirmed through testing.

Exclusion Criteria

Unable to undergo an 18F-DOPA-PET scan

Unable to undergo MRI scans with contrast

I am not using or willing to use birth control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients undergo either short course RT for 5-10 fractions over 1-2 weeks or standard course RT for 15-30 fractions over 3-6 weeks, with concurrent temozolomide administration

1-6 weeks

Multiple visits (in-person) for radiation therapy

Adjuvant Therapy

Patients receive temozolomide on days 1-5 every 28 days for up to 5-6 cycles post-radiation

5-6 months

Monthly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 2 months for the first year, every 3 months for the second year, every 4 months for the third year, then annually

Treatment Details

Interventions

• Accelerated Hypofractionated Radiation Therapy

Trial Overview The SAGA Study is testing if short course radiotherapy (RT) can be as effective as standard RT for glioblastoma treatment. It involves higher doses over fewer sessions which may reduce side effects while targeting tumor cells more aggressively than conventional methods.

Participant Groups

Group I: Arm A (short course RT) Experimental Treatment 9 Interventions

Patients undergo short course RT for 5-10 fractions over 1-2 weeks on study. Patients also receive temozolomide PO on days 1-5 every 28 days during radiation therapy. Starting one month post-radiation, patients continue temozolomide on days 1-5 every 28 days for up to 5 adjuvant cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT with 18-F-DOPA administered IV prior to RT on study, and undergo MRI prior to RT and throughout the trial. Patients may optionally undergo blood sample collection during screening and on the trial.

Group II: Arm B (standard course RT) Active Control 9 Interventions

Patients undergo standard course RT for 15-30 fractions over 3-6 weeks on study. Patients also receive temozolomide PO QD concurrently with radiation therapy and for up to 6 adjuvant cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT with 18-F-DOPA administered IV prior to RT on study, and undergo MRI prior to RT and throughout the trial. Patients may optionally undergo blood sample collection during screening and on the trial.

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

Approved in United States as Accelerated Hypofractionated Radiation Therapy for:

• Glioblastoma

Approved in European Union as Accelerated Hypofractionated Radiation Therapy for:

• Glioblastoma

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

A new survival score was developed for glioblastoma patients based on 10 factors, significantly improving the accuracy of predicting overall survival (OS) compared to previous models, achieving 100% accuracy for predicting death within 12 months.

Key factors for better local control and overall survival included having only one lesion, MGMT promoter methylation, and better performance status, which can help tailor radiotherapy approaches for individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Patients With Glioblastoma Who May Benefit from Hypofractionated Radiotherapy. Zemskova, O., Yu, NY., Trillenberg, P., et al.[2023]

In a study of 85 adult patients with cerebral glioblastoma, those receiving hypofractionated radiation therapy (5 Gy twice a week) showed better survival rates compared to those receiving conventional radiation therapy, particularly in patients with tumors in the frontal lobe.

The use of misonidazole in the hypofractionated group was associated with improved survival, suggesting it may enhance the effectiveness of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiation therapy of adult cerebral glioblastoma:]. Hayakawa, K., Arai, M., Niibe, H., et al.[2013]

A study involving 158 patients with glioblastoma multiforme (GBM) compared hyperfractionated radiotherapy (hf-rt) and accelerated-hyperfractionated radiotherapy (ahf-rt) to conventional radiotherapy (cf-rt) and found no significant difference in survival rates, with median survival ranging from 7 to 10 months.

The accelerated-hyperfractionated radiotherapy (ahf-rt) reduced treatment time to 4 weeks without compromising survival or increasing toxicity, suggesting it may be a suitable option for patients who cannot undergo more aggressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperfractionated and accelerated-hyperfractionated radiotherapy for glioblastoma multiforme. Nieder, C., Nestle, U., Ketter, R., et al.[2022]

Hypofractionated radiation therapy combined with temozolomide is a safe and effective treatment for elderly and frail glioblastoma patients with poor prognostic factors, showing a progression-free survival rate of 60% at 6 months and a median overall survival of 7 months.

The study involved 17 patients, with no severe acute toxicities reported, indicating that this treatment approach can be well-tolerated and may offer a cost-effective alternative to standard fractionation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiation therapy and temozolomide in patients with glioblastoma and poor prognostic factors. A prospective, single-institution experience. Jablonska, PA., Diez-Valle, R., Pérez-Larraya, JG., et al.[2020]

In a study of 277 glioblastoma patients, conventional fractionated radiotherapy (CF-RT) was found to provide significantly better local control and overall survival compared to hypo-fractionated radiotherapy (HF-RT), particularly in patients with a Karnofsky Performance Status (KPS) of 70 or lower and unifocal tumors.

While CF-RT generally showed better outcomes, the study suggests that certain selected patients, especially those who are elderly or frail, may still benefit from HF-RT, indicating a need for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypo-fractionated Radiotherapy (HF-RT) Versus Conventionally Fractionated Radiotherapy (CF-RT) for Glioblastoma. Zemskova, O., Pedachenko, E., Yu, NY., et al.[2023]

Hypofractionated radiation therapy (HFRT) shows promise for glioblastoma patients by delivering higher doses in a shorter treatment time, leading to increased cell death while maintaining acceptable toxicity levels.

Interestingly, some studies suggest that patients who develop radiation necrosis at the tumor site may experience improved survival, challenging the traditional classification of this condition as severe toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hypofractionated radiotherapy for glioblastoma: changing the radiation treatment paradigm]. Gerasimov, VA., Boldyreva, VV., Datsenko, PV.[2018]

In a study of 131 glioblastoma patients, accelerated hyperfractionated radiotherapy (AHFRT) did not show a significant improvement in progression-free survival (PFS) or overall survival (OS) compared to normofractionated radiotherapy (NFRT), with median OS of 10 months for AHFRT and 15 months for NFRT.

Both treatment regimens had similar acute toxicity profiles, suggesting that AHFRT may offer logistical benefits, such as shorter hospitalization times, without compromising safety, warranting further investigation in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated hyperfractionation plus temozolomide in glioblastoma. Kaul, D., Florange, J., Badakhshi, H., et al.[2018]

The hypofractionated accelerated radiotherapy regimen for glioblastoma multiforme (GBM) was well tolerated among 25 patients, with limited acute toxicity and no late toxicity observed, suggesting it is a safe treatment option.

Despite the treatment's feasibility and a reduction in overall treatment time, the study found no significant survival advantage, with a median survival of 9.5 months and a 1-year survival rate of 40%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of hypofractionated intensity-modulated irradiation in the treatment of glioblastoma multiforme: preliminary results of a prospective trial. Sultanem, K., Patrocinio, H., Lambert, C., et al.[2019]

In a study of 41 young, fit patients with glioblastoma, hypofractionated radiation therapy (HF-RT) showed similar overall survival (OS) and progression-free survival (PFS) compared to conventionally fractionated radiation therapy (CF-RT), suggesting that HF-RT is an effective alternative.

Both HF-RT and CF-RT had low rates of severe side effects, with Grade 3 radionecrosis rates of 6.7% and 7.7%, indicating that HF-RT may provide a safer and more convenient treatment option without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderately hypofractionated versus conventionally fractionated radiation therapy with temozolomide for young and fit patients with glioblastoma: an institutional experience and meta-analysis of literature. Chidley, P., Shanker, M., Phillips, C., et al.[2022]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Identification of Patients With Glioblastoma Who May Benefit from Hypofractionated Radiotherapy. [2023]

2. Japan pubmed.ncbi.nlm.nih.gov

[Radiation therapy of adult cerebral glioblastoma:]. [2013]

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

Hyperfractionated and accelerated-hyperfractionated radiotherapy for glioblastoma multiforme. [2022]

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

Hypofractionated radiation therapy and temozolomide in patients with glioblastoma and poor prognostic factors. A prospective, single-institution experience. [2020]

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

Hypo-fractionated Radiotherapy (HF-RT) Versus Conventionally Fractionated Radiotherapy (CF-RT) for Glioblastoma. [2023]

6. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Hypofractionated radiotherapy for glioblastoma: changing the radiation treatment paradigm]. [2018]

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

Accelerated hyperfractionation plus temozolomide in glioblastoma. [2018]

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

The use of hypofractionated intensity-modulated irradiation in the treatment of glioblastoma multiforme: preliminary results of a prospective trial. [2019]

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

Moderately hypofractionated versus conventionally fractionated radiation therapy with temozolomide for young and fit patients with glioblastoma: an institutional experience and meta-analysis of literature. [2022]