Radiation Therapy for Recurrent Brain Tumors

Overseen By Theresa C Cooley Zgela, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Bevacizumab, Temozolomide, Cytotoxic chemotherapy, others

Disqualifiers: Pregnancy, Radiation sensitivity, Uncontrolled illness, others

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

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

Compensation: Varies

Number of Visits: 5

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find a safe way to use radiation therapy for brain tumors that have returned after initial treatment for glioblastoma, an aggressive brain cancer. Researchers are testing different radiation schedules to determine which is safest and most effective. This trial may suit adults with grade 4 glioblastoma that has recurred after previous radiation therapy. Participants will receive radiation treatments multiple times a week and will be closely monitored to evaluate their health and the treatment's effects. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new approach.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot have had certain treatments like Bevacizumab, Temozolomide, or cytotoxic chemotherapy within 2-3 weeks before starting the study. It's best to discuss your current medications with the trial team.

What prior data suggests that this radiation therapy is safe for treating recurrent brain tumors?

Research has shown that treatments like the one in this trial, which involve re-administering radiation, have been successful in other studies. For instance, one study found that delivering larger doses of radiation over fewer sessions can be effective for patients with recurring brain tumors.

Regarding safety, these treatments are generally well-tolerated. Many studies report that most patients complete the treatment without serious side effects. However, some patients might experience fatigue or skin irritation at the radiation site.

This trial is in its early stage, focusing primarily on finding the safest way to administer the radiation. While existing evidence supports the safety of similar treatments, this trial will help determine its effectiveness for recurring glioblastoma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores a new radiation therapy technique for recurrent brain tumors called hypofractionation re-irradiation. Unlike standard treatments like surgery, conventional radiation, or chemotherapy, this approach focuses on delivering higher doses of radiation over fewer sessions. This could potentially reduce the overall treatment time and minimize side effects. Moreover, the trial is testing different dose levels to find the maximum tolerated dose, which could lead to more effective and personalized treatment options for patients with recurring brain tumors.

What evidence suggests that this radiation therapy is effective for recurrent brain tumors?

Research has shown that hypofractionated stereotactic re-irradiation can effectively treat worsening glioblastoma, a type of brain cancer. This trial explores different approaches to hypofractionated re-irradiation. In Arm 1, participants receive fraction size escalation of three planned re-irradiation dose levels. Arm 2 determines the maximum tolerated dose (MTD) of re-irradiation. Studies have found that this method can shrink tumors while minimizing harm to nearby healthy brain tissue. In some trials, patients who received this treatment had better outcomes, especially if their cancer returned more than 14 months after their initial treatment. Evidence also suggests that this approach can help lower the risk of tumor recurrence. Overall, hypofractionated re-irradiation offers hope for people with recurring glioblastoma. ^{1 5 6 7 8}

Who Is on the Research Team?

Peter GK Mathen, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a type of brain cancer called grade 4 glioblastoma, which has returned after initial radiation therapy. Participants must have completed their first round of treatment and be in good enough health to undergo further radiation.

Inclusion Criteria

- Absolute neutrophil count (ANC) greater than or equal to 1,000/microL

I am mostly able to care for myself.

My organs and bone marrow work well.

Exclusion Criteria

I have not started the study therapy yet.

I may have a condition that makes me sensitive to radiation.

I cannot have an MRI or gadolinium contrast for any reason.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Re-irradiation Treatment

Participants undergo re-irradiation treatment 4 times per week for 1, 2, or 3 weeks, depending on the assigned dose level.

1-3 weeks

4 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up visits 1 month after treatment, then every 2 months for 6 months, and every 3 months up to 3 years. Remote follow-up continues for an additional 2 years.

5 years

In-person visits and remote follow-ups

What Are the Treatments Tested in This Trial?

Interventions

• Hypofractionation Trial of Re-irradiation

Trial Overview The study is testing different schedules of re-irradiation (radiation therapy) on patients whose glioblastoma has recurred. The goal is to find the safest way to administer this treatment by varying the frequency and duration over one, two, or three weeks.

How Is the Trial Designed?

Group I: 2/Arm 2 Experimental Treatment 1 Intervention

MTD of re-irradiation dose.

Group II: 1/Arm 1 Experimental Treatment 1 Intervention

Fraction size escalation of 3 planned re-irradiation dose levels.

Hypofractionation Trial of Re-irradiation is already approved in European Union, United States for the following indications:

Approved in European Union as Re-irradiation for:

• Recurrent glioblastoma multiforme (GBM)

Approved in United States as Re-irradiation for:

• Recurrent glioblastoma multiforme (GBM)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 75 patients with 108 brain metastases treated with hypofractionated stereotactic radiotherapy (hfSRT), a cumulative biological equivalent dose (EQD2) of ≥35 Gy was found to be the most effective for achieving better local control of tumors, with a median local control time of 14.9 months compared to 3.4 months for doses ≤35 Gy.

While higher doses (EQD2 >35 Gy) were associated with increased rates of mild toxicity (31% vs. 8.3% for ≤35 Gy), the treatment was still considered safe, indicating that hfSRT can effectively manage limited brain metastases with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated stereotactic radiotherapy of limited brain metastases: a single-centre individualized treatment approach. Märtens, B., Janssen, S., Werner, M., et al.[2022]

In a study involving 20 patients with recurrent malignant gliomas, hypofractionated stereotactic radiotherapy (H-SRT) demonstrated a low toxicity profile, with no grade 3 toxicities or reoperations required due to treatment-related complications.

The study found that higher total doses of H-SRT (30 Gy and 35 Gy) were associated with a significantly better response rate (79%) compared to lower doses, suggesting that dose escalation could enhance treatment efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose escalation study of hypofractionated stereotactic radiotherapy as salvage therapy for persistent or recurrent malignant glioma. Hudes, RS., Corn, BW., Werner-Wasik, M., et al.[2022]

Stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (HFSRT) are effective treatment options for brain metastases, but their use in patients with life-limiting diseases remains a topic of debate.

This review highlights the need for careful consideration of the indications and challenges associated with SRS and HFSRT to optimize patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery and stereotactic radiotherapy for brain metastases. Halasz, LM., Rockhill, JK.[2022]

Hypofractionated radiosurgery (hfSRS) is an effective alternative to single-fraction radiosurgery (SRS) for treating brain metastases, benign tumors, and arteriovenous malformations (AVMs), especially when lesions are too large or poorly located for single-fraction treatment.

Recent literature indicates that local control rates and AVM obliteration rates with hfSRS are comparable to those achieved with single-fraction SRS, and the associated toxicities are similar, making hfSRS a safe and effective option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of Hypofractionated Radiosurgery for the Treatment of Intracranial Lesions Unsuitable for Single-Fraction Radiosurgery. Zhong, J., Press, RH., Olson, JJ., et al.[2019]

Fractionated stereotactic radiotherapy (FSRT) was evaluated in 172 patients with recurrent gliomas, showing it is well tolerated and may improve survival, particularly in lower-grade tumors.

Median survival after reirradiation was 8 months for glioblastoma multiforme (GBM), 16 months for WHO grade 3 tumors, and 22 months for grade 2 gliomas, indicating that histologic grading and time to progression are key factors influencing outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of fractionated stereotactic reirradiation in recurrent gliomas: long-term results in 172 patients treated in a single institution. Combs, SE., Thilmann, C., Edler, L., et al.[2022]

Hypofractionated stereotactic radiotherapy (HFSRT) is a safe treatment option for patients with recurrent malignant glioma, showing a median overall survival of 9.3 months, with some patients surviving over 77 months.

Patients receiving a total dose of 30 Gy had a longer overall survival (11.1 months) compared to those receiving less than 30 Gy (7.4 months), suggesting that higher doses may improve outcomes without increasing the risk of radiation necrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated stereotactic re-irradiation: treatment option in recurrent malignant glioma. Vordermark, D., Kölbl, O., Ruprecht, K., et al.[2022]

Hypofractionated stereotactic radiotherapy (hfSRT) demonstrated significant efficacy in treating irresectable brain metastases, with a complete remission rate of 66.7% and a median survival of 11 months among 51 patients studied over a median follow-up of 7 months.

The treatment's safety profile indicates that side effects are linked to the volume of normal brain tissue receiving more than 4 Gy per fraction, with a threshold of 20 cc suggested to minimize risks of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of hypofractionated stereotactic radiotherapy for brain metastases: results and toxicity. Ernst-Stecken, A., Ganslandt, O., Lambrecht, U., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11023988/

Hypofractionated stereotactic re-irradiation for progressive ... Hypofractionated SRT is an effective treatment approach for patients with progressive glioblastoma. Younger patients who progressed later than 14 months, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12468168/

Hypo-Fractionated Stereotactic Radiosurgery for the ... This technique maintains high tumor control while minimizing radiation toxicity to nearby brain structures. This review summarizes the current ...

3. thegreenjournal.com thegreenjournal.com/article/S0167-8140(24)04358-5/fulltext

ESTRO/EANO recommendation on reirradiation of ... Concurrent stereotactic radiosurgery and bevacizumab in recurrent malignant gliomas: a prospective trial. Int J Radiat Oncol Biol Phys. 2013; 86:873-889. Full ...

4. academic.oup.com academic.oup.com/neuro-oncology/advance-article/doi/10.1093/neuonc/noaf182/8220627

Results of the ESTRON randomized phase 2 trial | Neuro ... Whole-brain radiotherapy (WBRT) reduces recurrence risk but impairs neurocognition. Hypofractionated stereotactic radiotherapy of the cavity ( ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1278321825000964

Hypofractionated radiotherapy of central nervous system ... The use of hypofractionated radiotherapy for central nervous system tumours is expanding, particularly due to the increase in reirradiation situations.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2405630825001302

Prognostic factors, patterns of failure and re-irradiation in ... Re-fSRT may improve survival in highly selected patients with limited recurrent BMs. Abstract. Background. Hypofractionated stereotactic ...

7. mdpi.com mdpi.com/2072-6694/17/18/3026

Hypo-Fractionated Stereotactic Radiosurgery for the ... The 12-month local control rates for brain metastases ≥3 cm were 54% after single-fraction SRS and 73% after HySRS (p = 0.02). The 1-year cumulative incidence ...

8. ar.iiarjournals.org ar.iiarjournals.org/content/36/10/4985

Re-irradiation for Recurrent Primary Brain Tumors In a different study, 3-year local control was 89% (12 patients, fractionated stereotactic re-irradiation) and median event-free survival 3.4 years (87). In 6 ...