MR-Guided Adaptive Radiotherapy + Temozolomide for Glioblastoma

Overseen By Michelle Kim, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Michigan Rogel Cancer Center

Disqualifiers: Recurrent glioma, Brainstem tumor, Severe disease, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new approach to radiation therapy, combined with the chemotherapy drug Temozolomide, can extend survival for individuals with glioblastoma, an aggressive brain cancer. The trial targets more precise radiation delivery to difficult-to-treat tumor areas, aiming to improve survival compared to standard treatments. It seeks participants recently diagnosed with glioblastoma who have not yet undergone radiation. Those diagnosed with this type of brain cancer, without spread to areas like the brainstem, may find this trial suitable. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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. Please consult with the study team for guidance.

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 study team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that temozolomide (TMZ) is generally safe for treating glioblastoma, a type of brain cancer. Studies indicate that TMZ can help patients, including older ones, live longer. However, some individuals might experience blood-related side effects, such as anemia or low white blood cell counts.

The dose-intensified radiotherapy is currently in a Phase 2 trial, which means researchers are still studying its safety. Phase 2 trials have suggested some safety in earlier research, but more information is needed to fully understand its effects.

In summary, TMZ has a strong safety record, while the intensified radiotherapy is still under investigation for its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for glioblastoma?

Researchers are excited about dose-intensified radiotherapy for glioblastoma because it combines advanced imaging and targeted radiation in a way that current treatment options do not. Unlike standard therapies that use fixed radiation plans, this approach is adaptive, meaning it can adjust to changes in the tumor's size and shape in real-time, guided by MRI. This precision aims to maximize the radiation dose to the cancer cells while minimizing damage to surrounding healthy tissue, potentially improving outcomes and reducing side effects.

What evidence suggests that dose-intensified radiotherapy and temozolomide could be effective for glioblastoma?

Research shows that adding temozolomide to radiation therapy helps glioblastoma patients live longer. Studies have found that this combination increases the average survival time compared to using radiation alone. Specifically, one study revealed that 70% of patients who received both treatments were alive after 10 years, compared to 47% of those who only had radiation. Additionally, using temozolomide for a longer period has been linked to better survival without causing more severe side effects. In this trial, patients will receive dose-intensified, adaptive photon radiation therapy. Although research on MR-guided adaptive radiotherapy is still developing, this method aims to more accurately target high-risk tumor areas, potentially enhancing treatment effectiveness. ^{1 3 4 6 7}

Who Is on the Research Team?

Michelle Kim, MD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed glioblastoma who can give informed consent, follow study procedures, and have a life expectancy of at least 12 weeks. They should be in good physical condition (Karnofsky score ≥70), have adequate organ function, and agree to use contraception if applicable. The tumor must be ≤5 cm in diameter and patients must enroll within 6 weeks post-surgery.

Inclusion Criteria

My blood, liver, and kidney functions meet the required levels for the trial.

I have a newly diagnosed high-grade brain tumor.

I registered for the trial within 6 weeks after my last surgery.

Exclusion Criteria

I have had radiation therapy on my head or neck that overlaps with current treatment areas.

My MRI shows cancer in more than one part of an organ.

I have been cancer-free for at least 3 years, except for non-melanoma skin cancer or low-risk cancers not needing treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive dose-intensified, adaptive photon radiation therapy

6-8 weeks

Chemotherapy

Concurrent administration of Temozolomide with radiation therapy

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular visits for monitoring and assessments

Long-term follow-up

Participants are monitored for overall survival and quality of life

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Dose-Intensified Radiotherapy
• Temozolomide

Trial Overview

The study tests if intensified radiation therapy targeted at high-risk tumor areas during treatment improves survival in glioblastoma patients compared to standard chemoradiotherapy. It includes dose-intensified radiotherapy with concurrent temozolomide followed by adjuvant temozolomide.

How Is the Trial Designed?

Group I: Patients with Newly Diagnosed Glioblastoma Experimental Treatment 3 Interventions

Patients will receive dose-intensified, adaptive photon radiation therapy

Dose-Intensified Radiotherapy is already approved in United States, European Union for the following indications:

Approved in United States as Temodar for:

• Glioblastoma
• Anaplastic astrocytomas

Approved in European Union as Temodal for:

• Glioblastoma
• Anaplastic astrocytomas

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

Published Research Related to This Trial

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]

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 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]

Temozolomide (TMZ) was found to effectively radiosensitize two out of three human glioblastoma multiforme (GBM) cell lines when combined with single-dose gamma-irradiation, indicating its potential to enhance the effectiveness of radiation therapy.

In a study involving three genetically characterized GBM cell lines, TMZ demonstrated an additive effect with fractionated irradiation, particularly showing a significant reduction in surviving cells in the AMC 3046 cell line, suggesting that TMZ can improve treatment outcomes for certain GBM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential radiosensitizing potential of temozolomide in MGMT promoter methylated glioblastoma multiforme cell lines. van Nifterik, KA., van den Berg, J., Stalpers, LJ., et al.[2018]

In a study involving 16 patients with newly diagnosed glioblastoma multiforme, the combination of intensity-modulated radiotherapy (IMRT) and temozolomide (TMZ) was found to be tolerable, with a median survival of 16.2 months, indicating potential efficacy in this patient population.

The study demonstrated that escalating the IMRT dose to 6 Gy per fraction was achievable without reaching the maximal tolerated dose, suggesting that higher doses may be safely administered in selected patients with smaller tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of hypofractionated intensity-modulated radiotherapy with temozolomide chemotherapy for patients with newly diagnosed glioblastoma multiforme. Chen, C., Damek, D., Gaspar, LE., et al.[2018]

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 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]

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