Radiation Therapy + Temozolomide for Brain Tumor

Recruiting at 167 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

540 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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 used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether radiation therapy is more effective when given together with or without temozolomide in treating patients with low-grade glioma. PURPOSE: This randomized phase III trial is studying radiation therapy so see how well it works when given together with or without temozolomide in treating patients with low-grade glioma.

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.

What data supports the effectiveness of the treatment Radiation Therapy + Temozolomide for Brain Tumor?

Research shows that combining intensity-modulated radiation therapy (IMRT) with temozolomide (TMZ) improves outcomes for brain tumors. In patients with glioblastoma multiforme, those receiving this combination had a median survival of 17.4 months, which is better than the 14.6 months seen in a large trial of similar treatments. Additionally, for brain metastases from lung adenocarcinoma, the combination led to a significant objective response rate of 77.8% and improved quality of life. ^{1 2 3 4 5}

Is the combination of radiation therapy and temozolomide safe for treating brain tumors?

The combination of radiation therapy and temozolomide has been studied for safety in various brain conditions, including brain metastases and gliomas. Common side effects reported include neutropenia (low white blood cell count), anemia (low red blood cell count), vomiting, fatigue, and dizziness, but severe blood-related side effects were not observed. Overall, the treatment is considered safe with manageable side effects. ^{1 2 4 6 7}

How does the treatment of Radiation Therapy + Temozolomide for Brain Tumor differ from other treatments?

This treatment combines radiation therapy with temozolomide, a drug that enhances the effectiveness of radiation by making cancer cells more sensitive to it. The use of intensity-modulated radiation therapy (IMRT) allows for precise targeting of the tumor, minimizing damage to surrounding healthy tissue, and when combined with temozolomide, it has shown improved response rates and quality of life in patients compared to radiation alone. ^{1 2 4 8 9}

Research Team

David Schiff, MD

Principal Investigator

University of Virginia

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Intensity-modulated radiation therapy combined with concomitant temozolomide for brain metastases from lung adenocarcinoma. [2020]

2. China pubmed.ncbi.nlm.nih.gov

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

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

Improved outcomes with intensity modulated radiation therapy combined with temozolomide for newly diagnosed glioblastoma multiforme. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Safety and efficacy of three-dimensional conformal radiotherapy combined with temozolomide in treatment of diffuse brainstem gliomas]. [2018]

5. Pakistan pubmed.ncbi.nlm.nih.gov

Clinical efficacy of early postoperative intensity-modulated radiotherapy combined with Temozolomide chemotherapy in the treatment of patients with malignant glioma. [2022]

6. United States 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. [2018]

7. China pubmed.ncbi.nlm.nih.gov

Phase II trial of temozolomide and reirradiation using conformal 3D-radiotherapy in recurrent brain gliomas. [2022]

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

Effect of Temozolomide Combined with Intensity Modulated Radiation Therapy on Serum Factor, Immune Function and Clinical Efficacy in Postoperative Glioma Patients. [2023]

9. Cyprus pubmed.ncbi.nlm.nih.gov

Benefit and outcome of using temozolomide-based chemoradiotherapy followed by temozolomide alone for glioblastoma in clinical practice. [2019]