Adaptive Radiotherapy for Glioblastoma

(UNITED-3 Trial)

Overseen By Jay Detsky, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Disqualifiers: Other malignancies, Leptomeningeal dissemination, 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: Unknown

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering radiation therapy to individuals with glioblastoma, a type of brain cancer. The researchers aim to determine if this adaptive, two-phase radiation approach surpasses the standard method in controlling the cancer, improving survival rates, and maintaining quality of life. The study seeks participants with confirmed glioblastoma who have undergone a biopsy or surgery within the last 12 weeks and are eligible for long-course radiation treatment alongside other systemic therapies, such as Temodar (also known as Temodal or TMZ). As an unphased trial, it offers a unique opportunity to contribute to innovative research that could enhance treatment options for glioblastoma.

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 might be best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this adaptive, two-phase RT is safe for glioblastoma patients?

Research has shown that adaptive, two-phase radiotherapy (RT) for glioblastoma is generally safe. In one study, doctors targeted the tumor more precisely to protect healthy tissue. The results were positive, indicating that patients tolerated the treatment well.

Another study tested adaptive RT with increased doses tailored to individual needs. This study also found no major safety issues, suggesting that patients managed the treatment well.

Overall, while no major safety concerns have been reported so far, everyone can react differently. It is important to discuss potential risks with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about adaptive radiotherapy for glioblastoma because it offers a personalized approach to treatment. Unlike traditional radiotherapy, which follows a fixed plan, adaptive radiotherapy adjusts based on real-time changes in the tumor and surrounding tissues. This two-phase technique allows for more precise targeting of cancer cells while minimizing damage to healthy tissue. By tailoring the treatment to the patient's specific needs, there's potential for improved outcomes and reduced side effects, making it an innovative step forward in glioblastoma care.

What evidence suggests that this adaptive, two-phase RT is effective for glioblastoma?

Research suggests that a new type of two-phase radiation therapy (RT), which participants in this trial will receive, might improve treatment for glioblastoma, a type of brain cancer. One study found that this adaptive RT offers survival rates similar to standard treatments but with potentially fewer side effects. Another study showed that this method can better adjust to the changing size of tumors during treatment, which might help control the disease more effectively. Additionally, advanced imaging tools, like MR-Linac technology, may help target high-grade tumors more precisely, potentially enhancing treatment effectiveness. While these findings are encouraging, further research is needed to confirm these benefits. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed glioblastoma or grade 4 astrocytoma. They must have had a biopsy or surgery within the last 12 weeks, good blood counts and organ function, an expected survival of at least 12 weeks, and be in fair to good physical condition. Participants need to understand English for questionnaires and commit to treatment follow-up.

Inclusion Criteria

I had a biopsy or surgery for my condition within the last 12 weeks.

My diagnosis is glioblastoma or grade 4 astrocytoma.

My doctor thinks it's suitable for me to have radiation and medication treatment together.

Exclusion Criteria

I cannot have MRI contrast dyes due to an allergy or other health issue.

Contraindications to MRI examination

My cancer has spread to the lining of my brain and spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive adaptive radiation therapy with a smaller margin using MR-Linac technology

3 weeks

Daily visits for radiation therapy

Treatment Phase 2

Continuation of adaptive radiation therapy with adjustments based on daily MRI scans

3 weeks

Daily visits for radiation therapy

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

6-24 months

What Are the Treatments Tested in This Trial?

Interventions

• Adaptive, two-phase RT

Trial Overview The study tests an adaptive two-phase radiation therapy (RT) against standard RT in patients with glioblastoma. It aims to see if this new method improves tumor control, survival rates without disease progression, failure patterns, toxicity impact on neurological functions, and life quality.

How Is the Trial Designed?

Group I: Adaptive, two-phase RT Experimental Treatment 1 Intervention

Adaptive, two-phase RT is already approved in United States, European Union for the following indications:

Approved in United States as Temodar for:

• Glioblastoma multiforme
• Anaplastic astrocytoma

Approved in European Union as Temodal for:

• Glioblastoma multiforme
• Anaplastic astrocytoma
• Malignant glioma

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Published Research Related to This Trial

In a phase I clinical trial involving nine patients with glioblastoma, simultaneous integrated-boost intensity-modulated radiotherapy (SIB-IMRT) combined with temozolomide was found to be feasible and well tolerated up to a maximum dose of 80Gy.

No dose-limiting toxicities were observed at the highest dose level, indicating that this treatment combination may be safe for patients with malignant glioma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose escalation study using simultaneous integrated-boost IMRT with temozolomide in patients with unifocal glioblastoma. Truc, G., Bernier, V., Mirjolet, C., et al.[2018]

In a Phase I clinical trial involving 19 patients with glioblastoma, the maximum tolerated dose of fractionated intensity-modulated radiotherapy (IMRT) combined with temozolomide (TMZ) was determined to be 65 Gy, delivered in 25 fractions over 5 weeks, without any dose-limiting toxicities observed.

The treatment was well tolerated, with only mild to moderate (Grade 1-2) neurologic and skin toxicities reported, and no severe late neurologic toxicities, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose-escalation study (ISIDE-BT-1) of accelerated IMRT with temozolomide in patients with glioblastoma. Morganti, AG., Balducci, M., Salvati, M., et al.[2018]

In a study of 126 newly diagnosed glioblastoma patients, both standard dose radiotherapy (SDRT) and escalated dose radiotherapy (EDRT) combined with temozolomide (TMZ) showed similar overall survival (OS) and local progression-free survival (LPFS), with no statistically significant differences between the two treatments.

While the EDRT group had a median OS of 22 months compared to 14.9 months for SDRT, this difference was not statistically significant, indicating that further research with larger populations is needed to determine the true efficacy of EDRT in combination with TMZ.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective comparison of standard and escalated doses of radiotherapy in newly diagnosed glioblastoma patients treated with concurrent and adjuvant temozolomide. Guler, OC., Yıldırım, BA., Önal, C., et al.[2019]

In a Phase I clinical trial involving 37 patients with resected glioblastoma multiforme (GBM), the maximum tolerated dose (MTD) of volumetric modulated arc radiotherapy (VMAT-SIB) combined with standard dose temozolomide (TMZ) was determined to be 80 Gy delivered in 25 fractions over 5 weeks.

The trial identified dose-limiting toxicities at higher doses (82.5 Gy), with 29.7% of patients experiencing mild acute neurological toxicity and 8.1% experiencing severe toxicity, indicating that while the treatment can escalate doses, careful monitoring for side effects is crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Operative Accelerated-Hypofractionated Chemoradiation With Volumetric Modulated Arc Therapy and Simultaneous Integrated Boost in Glioblastoma: A Phase I Study (ISIDE-BT-2). Ferro, M., Ferro, M., Macchia, G., et al.[2022]

In a study of 78 patients with gliomas, combining 3-dimensional conformal radiotherapy with temozolomide resulted in a significantly higher 3-year survival rate of 41.38% compared to 20.83% for temozolomide alone and 20.00% for radiotherapy alone.

The combination therapy also improved progression-free survival time to 23.29 months and overall survival time to 25.75 months, while adverse reactions were reported to be mild and tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of 3-dimensional conformal radiotherapy combined with temozolomide for glioma]. Wang, L., Tu, Q., Zhou, W., et al.[2018]

In a study of 46 patients with newly diagnosed glioblastoma multiforme, hypofractionated high-dose intensity modulated radiation therapy (IMRT) combined with temozolomide (TMZ) resulted in a median overall survival of 20 months, indicating its efficacy in prolonging life for these patients.

No acute toxicity from the IMRT was observed, but radiation necrosis occurred in 20 patients, particularly in the subventricular zone, which was linked to longer survival, although it also negatively impacted the quality of life for some long-term survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 trial of hypofractionated high-dose intensity modulated radiation therapy with concurrent and adjuvant temozolomide for newly diagnosed glioblastoma. Iuchi, T., Hatano, K., Kodama, T., et al.[2018]

In a trial involving 40 glioblastoma patients, the maximum tolerated dose (MTD) of intensity-modulated radiotherapy (IMRT) was determined to be 70 Gy, delivered in 25 fractions, without unacceptable acute toxicity.

The study demonstrated that this high dose of radiation, combined with standard doses of temozolomide (TMZ), did not result in significant late neurological toxicity after a median follow-up of 25 months, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated intensity-modulated radiotherapy plus temozolomide in patients with glioblastoma: a phase I dose-escalation study (ISIDE-BT-1). Massaccesi, M., Ferro, M., Cilla, S., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2452109425001009

Comparative Outcomes of Standard Radiation Therapy ... Adaptive 5-fraction RT demonstrates comparable survival outcomes with conventional fractionation while reducing treatment-related travel burden. Further ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40058709/

Results From an Interim Analysis - PubMed - NIH In this single-arm phase 2 study, patients with newly diagnosed GBM after resection undergo dose-intensified chemoradiation targeting the residual ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8984129/

changes in target volume and organ at risk doses Results of this study confirm occurrence of target volume changes during RT for glioblastoma patients. An adaptive plan can provide better ...

4. link.springer.com link.springer.com/article/10.1007/s11060-025-05053-6

Advancements in adaptive MR-guided radiotherapy for ... This article explores the integration of MR-Linac technology into the treatment paradigm for high-grade gliomas, highlighting its potential to refine target ...

5. academic.oup.com academic.oup.com/neuro-oncology/article/26/Supplement_1/S3/7618749

Evolving concepts in margin strategies and adaptive ... The purpose of this review is to discuss margin strategies and the potential for adaptive RT for GBM, with a focus on the challenges and opportunities.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11994382/

Magnetic resonance imaging in glioblastoma radiotherapy The purpose of the study was to examine the safety of adaptive radiotherapy in glioblastoma, using a margin-reduction approach based on an interim magnetic ...

7. withpower.com withpower.com/trial/phase-glioblastoma-1-2023-2e5d0

Adaptive Radiotherapy for Glioblastoma (UNITED-3 Trial) Research shows that combining radiotherapy with temozolomide (a chemotherapy drug) has been studied for safety in patients with glioblastoma.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03970447

Study Details | NCT03970447 | A Trial to Evaluate Multiple ... GBM AGILE is an international, seamless Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed ...