606 Participants Needed

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
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

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.12345

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.46789

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.4581011

Who Is on the Research Team?

MP

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.
See 14 more

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.
See 22 more

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?
4Treatment groups
Experimental Treatment
Active Control
Group I: Arm C (proton beam radiation therapy)Experimental Treatment5 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 Treatment6 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 Control6 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 Control6 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

Find a Clinic Near You

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

Citations

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. [2018]
In Vitro Radiosensitizing Effects of Temozolomide on U87MG Cell Lines of Human Glioblastoma Multiforme. [2020]
Future directions for temozolomide therapy. [2019]
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]
Temozolomide and radiotherapy versus radiotherapy alone in high grade gliomas: a very long term comparative study and literature review. [2018]
The inhibition of proliferation and migration of glioma spheroids exposed to temozolomide is less than additive if combined with irradiation. [2018]
Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study. [2018]
Randomized phase II study of temozolomide and radiotherapy compared with radiotherapy alone in newly diagnosed glioblastoma multiforme. [2018]
Radiosensitization of Glioma Cells by Temozolomide (TMZ): A Colony Formation Assay. [2022]
10.United Statespubmed.ncbi.nlm.nih.gov
Early necrosis following concurrent Temodar and radiotherapy in patients with glioblastoma. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
Radiation therapy dose escalation for glioblastoma multiforme in the era of temozolomide. [2022]
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