Radiation Therapy + Temozolomide for Brain Tumor

Not currently recruiting at 168 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eastern Cooperative Oncology Group

Disqualifiers: Other malignancy, Uncontrolled infection, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of radiation therapy with or without the chemotherapy drug temozolomide in treating low-grade glioma, a type of brain tumor. The goal is to determine if combining these treatments can more effectively target and kill tumor cells compared to radiation alone. Suitable candidates for this trial include individuals with low-grade gliomas experiencing uncontrolled symptoms such as frequent headaches, seizures not managed by medication, or worsening symptoms on MRI scans. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients with uncontrolled seizures despite two different antiepileptic drug regimens are eligible, suggesting that continuing certain medications might be allowed. Please consult with the trial coordinators for specific guidance.

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

A previous study found temozolomide, a chemotherapy drug, to be a safe option for treating brain tumors like glioblastoma, which resembles low-grade glioma. Patients tolerated it well when combined with radiation therapy. Research has shown that the most common side effects were manageable and included tiredness, nausea, and some changes in blood counts.

The FDA has already approved temozolomide for certain brain cancers, confirming its well-known safety profile. Studies with children indicate that doses similar to those used in adults were generally well-tolerated. While some side effects can occur, they are usually not severe.

Radiation therapy uses high-energy x-rays to target the tumor, aiming to kill more tumor cells while protecting healthy tissue. This approach could result in fewer side effects compared to older types of radiation.

Overall, the combination of temozolomide and radiation therapy has a history of being well-tolerated, with typically manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of radiation therapy and temozolomide for brain tumors because this approach offers a targeted treatment option that enhances the effects of radiation. Unlike standard radiation therapies, which primarily rely on precise targeting to minimize damage to healthy tissue, this combination uses temozolomide to sensitize tumor cells, potentially making them more responsive to radiation. Additionally, temozolomide is administered orally, which can simplify the treatment process and improve patient compliance. This combination approach has the potential to improve outcomes by attacking the tumor from multiple angles, which could lead to better control of the disease and extended survival times for patients.

What evidence suggests that this trial's treatments could be effective for low-grade glioma?

Research has shown that combining temozolomide with radiation therapy may effectively treat certain brain tumors, such as low-grade gliomas. In this trial, one group of participants will receive both treatments. Specifically, studies have demonstrated that patients who received both treatments had a 10-year survival rate of 70%, compared to 47% for those who only received radiation therapy, which is the treatment for another group in this trial. Temozolomide directly kills tumor cells and may also extend the time patients live without cancer progression. Overall, this combined treatment could lead to better outcomes for people with this type of brain tumor. ^{6 7 8 9 10}

Who Is on the Research Team?

David Schiff, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for adults with low-grade glioma, a type of brain tumor. Participants must have symptoms like headaches or seizures, show tumor growth on MRIs, or be over 40 years old. They should be in good physical condition and not pregnant. People who only have well-controlled seizures or other specific health issues are excluded.

Inclusion Criteria

Your platelet count is at least 100,000 per cubic millimeter.

Your hematocrit level is equal to or greater than 30%.

Your bilirubin levels in the blood are not more than 2 times the normal limit.

Exclusion Criteria

I do not have any health conditions that would shorten my life to less than 5 years.

I haven't had treatments like radiation or chemotherapy for my brain tumor.

I have not had radiation therapy to my head that affected my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Patients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily 5 days a week for 5½ weeks

5.5 weeks

5 visits per week (in-person)

Chemotherapy

Patients receive concurrent oral temozolomide once daily for 5½ weeks, followed by temozolomide alone every 28 days for 12 courses

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• 3-dimensional conformal radiation therapy
• Intensity-modulated radiation therapy
• Temozolomide

Trial Overview The study is testing if radiation therapy works better alone or combined with temozolomide chemotherapy for treating low-grade glioma. Patients will randomly receive either just high-precision radiation therapy or the same radiation plus temozolomide.

How Is the Trial Designed?

Group I: Arm II Experimental Treatment 3 Interventions

Patients undergo radiotherapy as in arm I and receive concurrent oral temozolomide once daily for 5½ weeks. Beginning 28 days after completion of chemoradiotherapy, patients receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Group II: Arm I Active Control 2 Interventions

Patients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily 5 days a week for 5½ weeks (28 fractions).

Who Is Running the Clinical Trial?

Eastern Cooperative Oncology Group

Lead Sponsor

Trials

272

Recruited

153,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 9 patients with brain metastases from lung adenocarcinoma, the combination of intensity-modulated radiation therapy (IMRT) and temozolomide (TMZ) resulted in a high objective response rate of 77.8%, with one complete response and six partial responses, confirming the efficacy of this treatment approach.

Patients receiving the combination treatment experienced fewer severe adverse effects compared to those who only received IMRT, with no grade ≥3 hematologic toxicities reported, and an improvement in quality of life was noted, indicating that the addition of TMZ is both effective and relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy combined with concomitant temozolomide for brain metastases from lung adenocarcinoma. Li, J., Chai, X., Cao, Y., et al.[2020]

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]

In a study of 46 patients with newly diagnosed glioblastoma multiforme, hypofractionated high-dose intensity modulated radiation therapy (IMRT) combined with temozolomide (TMZ) resulted in a median overall survival of 20 months, indicating its efficacy in prolonging life for these patients.

No acute toxicity from the IMRT was observed, but radiation necrosis occurred in 20 patients, particularly in the subventricular zone, which was linked to longer survival, although it also negatively impacted the quality of life for some long-term survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 trial of hypofractionated high-dose intensity modulated radiation therapy with concurrent and adjuvant temozolomide for newly diagnosed glioblastoma. Iuchi, T., Hatano, K., Kodama, T., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9833842/

Temozolomide treatment outcomes and immunotherapy ... Temozolomide can have both beneficial and detrimental effects on immunotherapy efficacy by 1) reducing tumor burden by directly killing GBM, 2) increasing ...

2. ecog-acrin.org ecog-acrin.org/press-release-adding-the-chemotherapy-pill-temozolomide-to-radiation-therapy-improves-survival-in-adult-patients-with-glioma-a-slow-growing-type-of-brain-cancer/

Clinical trial finds that adding the chemotherapy pill ... “We found that the 10-year survival rate was 70% with the combined treatment with temozolomide chemotherapy and radiation, compared to 47% with ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2375282/

A rapid and systematic review of the effectiveness of ... The key results were that temozolomide may increase progression-free survival but has no significant impact on overall length of survival. The main effect from ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0753332223009654

Strategies increasing the effectiveness of temozolomide at ... Strategies increasing the efficacy of brain glioma TMZ therapy are reviewed. ... It was found that the outcomes of TMZ chemotherapy were improved in in vivo ...

5. mdpi.com mdpi.com/1718-7729/31/7/296

Temozolomide (TMZ) in the Treatment of Glioblastoma ... The response rate to therapy was 41% and the tumor control rate was 80%. In the 67 patients who completed chemoradiotherapy with TMZ, the median ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11275351/

Temozolomide (TMZ) in the Treatment of Glioblastoma ... Adjuvant therapy of TMZ after RT is a safe therapeutic option, and its efficacy seems to be higher than that of RT alone, although it largely ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2016/021029s031lbl.pdf

TEMODAR (temozolomide) Label - accessdata.fda.gov TEMODAR Capsules have been studied in 2 open- label studies in pediatric patients (aged 3-18 years) at a dose of 160 to 200 mg/m2 daily for 5 days every 28 days ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804906005077

Safety and pharmacokinetics of temozolomide using a ... The aims of this study were to determine the maximum tolerated dose (MTD), toxicity and pharmacokinetics of oral temozolomide administered over 42 d in ...

9. mayoclinic.org mayoclinic.org/drugs-supplements/temozolomide-oral-route/description/drg-20066228

Temozolomide (oral route) - Side effects & dosage Temozolomide is used to treat specific types of brain cancer (eg, glioblastoma multiforme, anaplastic astrocytoma) in patients whose tumors have returned.

10. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1437436/full

Comprehensive understanding of the adverse effects ... In a clinical trial involving 347 patients with malignant glioma treated with TMZ, the safety of TMZ was clearly evaluated, and the most common ...