High-Dose Radiation + Temozolomide for Glioblastoma

Recruiting at 258 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

606 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This randomized phase II trial studies how well dose-escalated photon intensity-modulated radiation therapy (IMRT) or proton beam radiation therapy works compared with standard-dose radiation therapy when given with temozolomide in patients with newly diagnosed glioblastoma. Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells and shrink tumors. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs, such as temozolomide, may make tumor cells more sensitive to radiation therapy. It is not yet known whether dose-escalated photon IMRT or proton beam radiation therapy is more effective than standard-dose radiation therapy with temozolomide in treating 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. 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 the combination of high-dose radiation and temozolomide generally safe for humans?

Temozolomide, when used with radiation therapy, is generally considered safe but can cause severe myelotoxicity (damage to the bone marrow, which can affect blood cell production) in some cases. It has a lower toxicity profile compared to some traditional chemotherapy drugs, but patients should be monitored for potential side effects. ^{1 2 3 4 5}

What makes the treatment of high-dose radiation and temozolomide unique for glioblastoma?

This treatment combines high-dose radiation with temozolomide, a chemotherapy drug that makes cancer cells more sensitive to radiation, potentially improving treatment effectiveness. Temozolomide is taken orally and is known for having fewer side effects compared to older chemotherapy drugs, making it a preferred option for patients with newly diagnosed glioblastoma. ^{4 6 7 8 9}

What data supports the effectiveness of the drug Temozolomide combined with radiation therapy for glioblastoma?

Research shows that combining Temozolomide with radiation therapy is more effective for treating high-grade brain tumors like glioblastoma than using radiation therapy alone. Temozolomide is a chemotherapy drug that has been shown to improve survival rates when used alongside radiation in patients with newly diagnosed glioblastoma. ^{4 5 8 10 11}

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.

I haven't had serious wounds, ulcers, fractures, or major surgeries in the last 28 days.

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

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

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 (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]

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 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]

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]

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]

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]

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]

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]

Citations

1. Greece pubmed.ncbi.nlm.nih.gov

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. [2018]

2. Iran pubmed.ncbi.nlm.nih.gov

In Vitro Radiosensitizing Effects of Temozolomide on U87MG Cell Lines of Human Glioblastoma Multiforme. [2020]

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

Future directions for temozolomide therapy. [2019]

4. England 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. [2020]

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

Temozolomide and radiotherapy versus radiotherapy alone in high grade gliomas: a very long term comparative study and literature review. [2018]

6. Greece 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. [2018]

7. United States 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. [2018]

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

Randomized phase II study of temozolomide and radiotherapy compared with radiotherapy alone in newly diagnosed glioblastoma multiforme. [2018]

9. Iran pubmed.ncbi.nlm.nih.gov

Radiosensitization of Glioma Cells by Temozolomide (TMZ): A Colony Formation Assay. [2022]

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

Early necrosis following concurrent Temodar and radiotherapy in patients with glioblastoma. [2022]

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

Radiation therapy dose escalation for glioblastoma multiforme in the era of temozolomide. [2022]