High-Dose Radiation + Temozolomide for Glioblastoma

Not currently recruiting at 266 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NRG Oncology

Must be taking: Temozolomide

Must not be taking: Temozolomide

Disqualifiers: Prior invasive malignancy, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 7-8 weeks for radiation therapy, up to 12 months for adjuvant temozolomide

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new methods for treating glioblastoma, a type of brain cancer. It compares various radiation therapies combined with temozolomide, an oral chemotherapy drug, to determine which method best shrinks tumors while minimizing damage to normal tissue. Individuals newly diagnosed with glioblastoma who have undergone surgery to remove the tumor may be suitable candidates, particularly if the remaining tumor is 5 cm or smaller. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that prior chemotherapy for a different cancer is allowed, except for temozolomide. It's best to discuss your current medications with the trial team to get a clear answer.

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

Research has shown that both proton beam radiation therapy and photon IMRT are generally safe for patients with glioblastoma. Proton beam therapy is well tolerated and may reduce side effects, such as memory and thinking problems, while maintaining or improving survival rates. Studies indicate it is as safe and effective as other radiation types. Photon IMRT, another form of targeted radiation, shows promise in delivering high doses directly to tumors while protecting healthy tissue. This approach can potentially lower the risk of serious side effects, such as damage to blood cells. Both treatments have demonstrated good safety records in past studies. Additionally, the drug temozolomide, used alongside these treatments, is FDA-approved for glioblastoma, indicating it is generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for glioblastoma because they explore innovative ways to enhance the effectiveness of radiation therapy. Unlike traditional options that primarily use standard-dose photon beam therapy, this trial investigates dose-escalated and intensified radiation techniques, both with photon IMRT and proton beam therapy. Proton beam therapy is particularly promising because it delivers higher doses of radiation directly to the tumor while sparing surrounding healthy tissues, potentially reducing side effects. Additionally, all treatment arms incorporate temozolomide, a chemotherapy drug, to enhance the treatment's overall effectiveness. This combination of advanced radiation techniques and chemotherapy could offer improved outcomes for patients battling this aggressive brain cancer.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

Research has shown that proton beam radiation therapy, one of the treatments studied in this trial, might help patients with newly diagnosed glioblastoma live longer compared to regular radiation therapy. One study found that high doses of proton beam therapy improved survival rates for these patients. Another treatment arm in this trial involves photon intensity-modulated radiation therapy (IMRT), which uses special techniques to deliver high doses of radiation directly to the tumor while protecting healthy tissue. This method may enhance treatment effectiveness by potentially killing more tumor cells. Both treatments, when combined with temozolomide (a drug that increases tumor cells' sensitivity to radiation), are being evaluated in this trial for their potential in treating glioblastoma. ^{2 4 6 7 8}

Who Is on the Research Team?

Minesh P Mehta

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

Adults with newly diagnosed glioblastoma located in the supratentorial compartment, who have undergone surgery and are able to undergo MRI scans. Participants must not have had prior invasive malignancies (except certain skin cancers) within 3 years or any previous chemotherapy for head and neck cancer (excluding temozolomide). They should be free from serious medical conditions that could interfere with the trial, not pregnant, willing to use contraception, and without a history of HIV/AIDS.

Inclusion Criteria

I can care for myself but cannot do normal activities without help.

History/physical examination within 28 days prior to step 2 registration

I had a brain MRI within 3 days after surgery showing a tumor or surgery area under 5 cm.

Exclusion Criteria

I have not used Gliadel wafers or similar treatments.

You have a very weak immune system due to a serious health condition.

- Any other major medical illnesses or psychiatric treatments that in the investigator's opinion will prevent administration or completion of protocol therapy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo radiation therapy (either standard-dose photon irradiation or dose-escalated photon IMRT/proton beam therapy) with concomitant temozolomide for 23-30 fractions over 5 days a week, followed by adjuvant temozolomide for up to 12 cycles.

7-8 weeks for radiation therapy, up to 12 months for adjuvant temozolomide

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up visits every 3 months for 1 year, every 4 months for another year, and then every 6 months thereafter.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Photon Beam Radiation Therapy
• Proton Beam Radiation Therapy
• Temozolomide

Trial Overview

The study is testing if higher doses of photon IMRT or proton beam radiation therapy can be more effective than standard-dose radiation when combined with temozolomide in treating glioblastoma. The goal is to see if these intensified treatments better target tumors while sparing healthy tissue and enhancing sensitivity to medication.

How Is the Trial Designed?

Group I: Arm C (proton beam radiation therapy) Experimental Treatment 5 Interventions

Patients undergo dose-escalated and -intensified proton beam therapy QD, 5 days a week for a total of 30 fractions. In all treatment arms, patients receive temozolomide PO QD on days 1-49 of radiation therapy. Beginning 4 weeks later, patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (photon IMRT) Experimental Treatment 6 Interventions

Patients undergo dose-escalated and -intensified photon IMRT QD, 5 days a week for a total of 30 fractions. In all treatment arms, patients receive temozolomide PO QD on days 1-49 of radiation therapy. Beginning 4 weeks later, patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Group III: Arm A1 (control) Active Control 6 Interventions

Patients undergo standard-dose photon irradiation using 3D-CRT or IMRT QD, 5 days a week for 23 fractions plus a boost of 7 additional fractions. In all treatment arms, patients receive temozolomide PO QD on days 1-49 of radiation therapy. Beginning 4 weeks later, patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Group IV: Arm A2 (control) Active Control 6 Interventions

Patients undergo standard-dose photon irradiation using 3D-CRT or IMRT as in Arm A1. In all treatment arms, patients receive temozolomide PO QD on days 1-49 of radiation therapy. Beginning 4 weeks later, patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Photon Beam Radiation Therapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Radiation Therapy for:

• Cancer treatment, including glioblastoma

Approved in European Union as Radiation Therapy for:

• Cancer treatment, including glioblastoma

Approved in Canada as Radiation Therapy for:

• Cancer treatment, including glioblastoma

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

Radiation Therapy Oncology Group

Collaborator

Trials

191

Recruited

64,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Temozolomide (TMZ) enhances the effectiveness of radiation therapy in treating glioblastoma cells, leading to a significant reduction in colony formation when combined with irradiation, compared to either treatment alone.

While irradiation was more toxic to glioma cells than TMZ, the combination of both treatments increased the sensitivity of glioma cells to radiation, suggesting a potential strategy for improving glioblastoma treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosensitization of Glioma Cells by Temozolomide (TMZ): A Colony Formation Assay. Babaloui, S., Najafi, M., Mozdarani, H., et al.[2022]

Temozolomide (TMZ) significantly enhances the effectiveness of gamma irradiation in treating glioma cells, demonstrating a notable increase in radiosensitivity compared to irradiation alone, based on in vitro studies with U87MG cell lines.

The study involved various treatment groups over 24, 48, and 72 hours, and the combination of TMZ and irradiation resulted in significantly lower cell viability, indicating a more effective treatment strategy for gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro Radiosensitizing Effects of Temozolomide on U87MG Cell Lines of Human Glioblastoma Multiforme. Borhani, S., Mozdarani, H., Babalui, S., et al.[2020]

In a phase II clinical trial involving 21 patients with newly diagnosed glioblastoma multiforme (GBM), the combination of temozolomide (TMZ) with radiotherapy resulted in a one-year survival rate of 58% and a median survival time of 15.7 months, indicating its efficacy in extending survival.

The treatment regimen was well-tolerated, with only mild to moderate non-hematological side effects and minimal severe hematological toxicity, suggesting that TMZ has a favorable safety profile compared to traditional chemotherapy agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. Lanzetta, G., Campanella, C., Rozzi, A., et al.[2018]

Temozolomide is primarily used for treating refractory central nervous system cancers like anaplastic astrocytoma and glioblastoma, but ongoing clinical trials are exploring its efficacy and safety in newly diagnosed gliomas and other types of tumors.

Research is also investigating different dosing schedules and combinations with other treatments, suggesting that temozolomide could be a versatile option in cancer therapy beyond its current approved uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. Yung, WK.[2019]

In a study of 130 patients with newly diagnosed glioblastoma multiforme (GBM), the combination of temozolomide (TMZ) with radiotherapy (RT) significantly improved median overall survival to 13.4 months compared to 7.7 months with RT alone.

The combination treatment also resulted in a longer median time to progression (10.8 months vs. 5.2 months) and a higher one-year progression-free survival rate (36.6% vs. 7.7%), indicating that TMZ enhances the effectiveness of RT in treating GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of temozolomide and radiotherapy compared with radiotherapy alone in newly diagnosed glioblastoma multiforme. Athanassiou, H., Synodinou, M., Maragoudakis, E., et al.[2018]

A study of 128 glioma patients over a period of more than 10 years showed that combining temozolomide (TMZ) with radiotherapy significantly improves long-term survival compared to radiotherapy alone.

The treatment with TMZ resulted in manageable side effects, with only 9% of patients experiencing grade 3 hematological toxicity, indicating that the combination therapy is both effective and relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide and radiotherapy versus radiotherapy alone in high grade gliomas: a very long term comparative study and literature review. Parisi, S., Corsa, P., Raguso, A., et al.[2018]

In a study of 27 patients with newly diagnosed high-grade gliomas, the combination of temozolomide (TMZ) and radiation therapy (RT) demonstrated promising efficacy, with a median overall survival of 19 months and a one-year survival rate of 81.2%.

The treatment was well tolerated with no drug toxicity-related mortality, indicating a favorable safety profile, especially in patients under 50 years old and those who had debulking surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The outcomes of concomitant radiation plus temozolomide followed by adjuvant temozolomide for newly diagnosed high grade gliomas: the preliminary results of single center prospective study. Shawky, H., Abo Hamar, AH., Galal, S., et al.[2020]

In a study of 51 patients with newly diagnosed glioblastoma, concurrent treatment with temozolomide (TMZ) and radiotherapy was found to be the new standard of care.

The occurrence of early necrosis in 14% of patients, without signs of tumor recurrence, suggests that TMZ may enhance the effectiveness of radiotherapy by acting as a radiosensitizer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early necrosis following concurrent Temodar and radiotherapy in patients with glioblastoma. Chamberlain, MC., Glantz, MJ., Chalmers, L., et al.[2022]

Temozolomide (TZM) combined with X-ray irradiation significantly inhibits the proliferation and migration of human glioma spheroids, with the most effective results seen at higher concentrations of TZM.

The study found that while the combination of TZM and radiation enhances the effects on glioma cells, the overall impact is less than what would be expected from simply adding the effects of each treatment alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The inhibition of proliferation and migration of glioma spheroids exposed to temozolomide is less than additive if combined with irradiation. Fehlauer, F., Muench, M., Richter, E., et al.[2018]

In a study of 87 newly diagnosed glioblastoma patients, only 5% experienced severe myelotoxicity during treatment with temozolomide (TMZ) and radiation therapy, indicating that while the risk exists, it is relatively low.

Factors such as female sex, low pretreatment platelet counts, and specific genetic markers were identified as potential predictors of severe myelotoxicity, suggesting that personalized treatment approaches could help mitigate risks in vulnerable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study. Lombardi, G., Rumiato, E., Bertorelle, R., et al.[2018]

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