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

30 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. 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.

What data supports the idea that MR-Guided Adaptive Radiotherapy + Temozolomide for Glioblastoma is an effective treatment?

The available research shows that MR-Guided Adaptive Radiotherapy combined with Temozolomide is being studied to find the best dose that patients can handle. These studies focus on how much of the treatment can be given safely, which is important for making sure it works well without causing too many side effects. While the studies don't directly compare this treatment to others, they suggest that using advanced radiotherapy techniques with Temozolomide might allow for higher doses that target the tumor more effectively, potentially improving outcomes for patients with glioblastoma. ^{1 2 3 4 5}

What data supports the effectiveness of this treatment for glioblastoma?

Several studies have explored the combination of advanced radiotherapy techniques with temozolomide (a chemotherapy drug) for treating glioblastoma, focusing on finding the maximum tolerated dose to improve treatment outcomes. These studies suggest that combining these therapies can potentially enhance the effectiveness of treatment by allowing higher doses to target the tumor while minimizing damage to healthy tissue. ^{1 2 3 4 5}

What safety data is available for MR-Guided Adaptive Radiotherapy and Temozolomide in treating glioblastoma?

The safety data for this treatment can be inferred from several studies. Phase I dose-escalation studies have been conducted to determine the maximum tolerated dose (MTD) of intensity-modulated radiotherapy (IMRT) combined with temozolomide (TMZ) in patients with glioblastoma. These studies, such as the ISIDE-BT-1 trial, evaluated the safety and efficacy of accelerated IMRT with concurrent and sequential-dose TMZ. Additionally, research on 3-dimensional conformal radiotherapy combined with TMZ has been conducted to assess safety and efficacy in gliomas. These studies collectively provide insights into the safety profile of combining radiotherapy with temozolomide for glioblastoma treatment. ^{1 2 3 6 7}

Is MR-Guided Adaptive Radiotherapy with Temozolomide safe for humans?

Research shows that combining radiotherapy with temozolomide has been studied for safety in patients with glioblastoma, focusing on finding the maximum tolerated dose. These studies suggest that the treatment is generally safe when doses are carefully managed. ^{1 2 3 6 7}

Is the treatment Dose-Intensified Radiotherapy with the drug Temozolomide promising for glioblastoma?

Yes, Dose-Intensified Radiotherapy with Temozolomide is promising for glioblastoma because studies are exploring how to safely increase the dose to improve treatment effectiveness. ^{1 2 3 4 8}

How is MR-Guided Adaptive Radiotherapy + Temozolomide different from other treatments for glioblastoma?

This treatment is unique because it combines MR-guided adaptive radiotherapy, which allows for precise targeting of the tumor, with temozolomide, a chemotherapy drug, to potentially enhance the effectiveness of the treatment by intensifying the radiation dose specifically to the tumor while sparing healthy tissue. ^{1 2 3 4 8}

What is the purpose of this trial?

This study will investigate whether or not intensified radiation therapy adapted during the radiation treatment course to high-risk, treatment-resistant tumor regions will improve overall survival in patients with newly diagnosed glioblastoma (GBM) compared to conventional chemoradiotherapy.

Research Team

Michelle Kim, MD

Principal Investigator

University of Michigan

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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 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 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]

References

1. France pubmed.ncbi.nlm.nih.gov

A phase I dose escalation study using simultaneous integrated-boost IMRT with temozolomide in patients with unifocal glioblastoma. [2018]

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

Accelerated intensity-modulated radiotherapy plus temozolomide in patients with glioblastoma: a phase I dose-escalation study (ISIDE-BT-1). [2022]

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

A phase I dose-escalation study (ISIDE-BT-1) of accelerated IMRT with temozolomide in patients with glioblastoma. [2018]

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

Phase I trial of hypofractionated intensity-modulated radiotherapy with temozolomide chemotherapy for patients with newly diagnosed glioblastoma multiforme. [2018]

5. Switzerland 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). [2022]

6. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of 3-dimensional conformal radiotherapy combined with temozolomide for glioma]. [2018]

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

Differential radiosensitizing potential of temozolomide in MGMT promoter methylated glioblastoma multiforme cell lines. [2018]

8. India 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. [2019]