Chemotherapy + Radiation for Brain Cancer

Overseen By Debra N Yeboa

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Metastatic disease, Prior malignancy, Prior cranial radiotherapy, 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: 6

Duration: 6 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well temozolomide and radiation therapy work in treating patients with IDH wildtype historically lower grade gliomas or non-histological molecular glioblastomas. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving chemotherapy with radiation therapy may kill more tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The goal of this clinical research study is to compare receiving new radiation therapy doses and volumes to the prior standard treatment for patients with historically grade II or grade III IDH wild-type gliomas, which may now be referred to as IDH wildtype molecular glioblastomas at some institutions. Receiving temozolomide in combination with radiation therapy may also help to control the disease.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

What data supports the effectiveness of the treatment combining chemotherapy and radiation for brain cancer?

Research shows that combining temozolomide (a chemotherapy drug) with radiation therapy is more effective for treating high-grade gliomas (a type of brain cancer) than using radiation alone. This combination has been associated with improved survival rates in patients. ^{1 2 3 4 5}

Is the combination of chemotherapy and radiation therapy safe for treating brain cancer?

The combination of chemotherapy (temozolomide) and radiation therapy has been studied for safety in treating brain metastases from lung cancer. It is generally well tolerated, with common side effects including fatigue, nausea, and mild blood-related issues. However, severe blood-related side effects have been reported in some cases. ^{1 2 3 6 7}

How is the treatment of chemotherapy and radiation for brain cancer different from other treatments?

This treatment combines radiation therapy with temozolomide, a drug that can enhance the effects of radiation by making cancer cells more sensitive to it. This combination is unique because it targets brain cancer more aggressively than radiation alone, potentially improving outcomes for patients with complex or hard-to-treat brain tumors. ^{1 2 3 8 9}

Research Team

Debra N. Yeboa

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with specific brain tumors called IDH wildtype gliomas or molecular glioblastomas, who haven't had chemotherapy or radiotherapy before. They should be able to undergo MRI scans, have a good performance status (able to carry out daily activities), and their blood counts and liver function tests need to be within certain limits.

Inclusion Criteria

I must have an MRI with contrast for my radiation therapy plan.

Bilirubin =< 1.5 upper limit of normal (ULN) (within 60 days prior to registration)

Serum creatinine < 1.5 mg/dl (within 60 days prior to registration)

Exclusion Criteria

My cancer has spread to the lining of my brain and spinal cord.

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

I was hospitalized for heart failure that affects my daily activities within the last year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive temozolomide orally daily and radiation therapy over 5 days a week for 6 weeks

6 weeks

5 visits per week (in-person)

Adjuvant Treatment

Participants receive temozolomide orally for 12 months in the absence of disease progression or unacceptable toxicity

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

Visits at 1, 3, 5, 7, 9, 12, 15, 18, 21, 24, 28, 32, and 36 months

Treatment Details

Interventions

• Radiation Therapy
• Temozolomide

Trial Overview The study is testing the effectiveness of combining temozolomide (a chemotherapy drug) with radiation therapy in treating these brain tumors. The goal is to see if this combination works better than previous standard treatments in controlling the disease.

Participant Groups

Group I: Treatment (temozolomide, radiation therapy) Experimental Treatment 4 Interventions

Patients receive temozolomide PO daily and radiation therapy over 5 days a week (weekdays only) for 6 weeks. Beginning 28 days after the last dose of radiation therapy, patients receive temozolomide PO for 12 months in the absence of disease progression or unacceptable toxicity.

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Whole-brain radiotherapy (WBRT) combined with temozolomide (TMZ) significantly improves the objective response rate in patients with brain metastases from non-small-cell lung cancer (NSCLC), with a relative risk of 1.43 based on a meta-analysis of 25 clinical trials.

However, this combination treatment also increases the risk of severe hematological (grade III-IV) and gastrointestinal toxicities compared to WBRT alone, indicating a need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response and safety of whole-brain radiotherapy plus temozolomide for patients with brain metastases of non-small-cell lung cancer: A meta-analysis. Han, J., Qiu, M., Su, L., et al.[2022]

In a phase II study involving 30 patients with brain metastases from non-small cell lung cancer (NSCLC), temozolomide (TMZ) was found to be an active and safe treatment option, with 10% of patients achieving an objective response, including two complete remissions.

No severe (grade 3 or 4) toxicities were reported, and all treatment-related adverse events were mild to moderate, indicating that TMZ can be administered without significant safety concerns in this heavily pre-treated patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: phase II study. Giorgio, CG., Giuffrida, D., Pappalardo, A., et al.[2018]

In a study of 128 patients with brain metastases from non-small cell lung cancer, synchronous stereotactic radiotherapy (SRT) combined with temozolomide (TMZ) and whole brain radiotherapy (WBRT) significantly improved overall survival (OS) and progression-free survival (PFS) compared to SRT with WBRT alone, with median OS of 13.1 months and PFS of 11.2 months in the TMZ group.

While the combination treatment led to a higher incidence of nausea and vomiting (67.2% vs. 43.8%), other adverse reactions were similar between the two groups, indicating that the treatment is generally tolerable despite some side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of synchronous stereotactic radiotherapy with temozolomide combined with whole brain radiotherapy in treating brain metastases originating from non-small cell lung cancer. Liu, P., Ren, R., You, D., et al.[2021]

In a study of 67 patients with newly diagnosed glioblastoma multiforme, the combination of temozolomide, thalidomide, and radiation therapy resulted in a median survival of 73 weeks, indicating a favorable outcome compared to those not receiving adjuvant chemotherapy.

The treatment was generally well tolerated, but the specific benefit of adding thalidomide to temozolomide remains uncertain, as the survival outcomes were similar to those seen with other chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of temozolomide and thalidomide with radiation therapy for newly diagnosed glioblastoma multiforme. Chang, SM., Lamborn, KR., Malec, M., 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 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]

Temozolomide (TMZ) is an effective oral treatment for malignant gliomas, providing significant survival benefits while being generally well tolerated by patients.

While most side effects of TMZ are mild to moderate, there is a risk of severe hematologic adverse events, such as myelodysplastic syndrome and aplastic anemia, which have been documented in the literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-related hematologic toxicity. Scaringi, C., De Sanctis, V., Minniti, G., et al.[2018]

Combining brain radiotherapy (RT) with temozolomide (TMZ) significantly improves the objective response rate (ORR) in patients with brain metastases, with an odds ratio of 2.27, indicating a better response to treatment compared to RT alone.

However, this combination treatment does not lead to a significant improvement in overall survival (OS) or progression-free survival (PFS), and it is associated with increased adverse effects, such as severe nausea and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis. Zhao, Q., Qin, Q., Sun, J., et al.[2018]

In a phase II trial involving 54 patients with complex brain metastases, the combination of hypofractionated stereotactic radiotherapy (HFSRT) and temozolomide (TMZ) was found to be well tolerated, with only a small percentage experiencing severe side effects.

The treatment resulted in a median overall survival of 17.4 months and high local control rates of 96% at 1 year and 82% at 2 years, suggesting it could significantly improve outcomes for patients with challenging brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Trial of Concurrent Temozolomide and Hypofractionated Stereotactic Radiotherapy for Complex Brain Metastases. Bi, N., Ma, Y., Xiao, J., et al.[2020]

References

1. Singapore pubmed.ncbi.nlm.nih.gov

Response and safety of whole-brain radiotherapy plus temozolomide for patients with brain metastases of non-small-cell lung cancer: A meta-analysis. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: phase II study. [2018]

3. Cyprus pubmed.ncbi.nlm.nih.gov

Efficacy of synchronous stereotactic radiotherapy with temozolomide combined with whole brain radiotherapy in treating brain metastases originating from non-small cell lung cancer. [2021]

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

Phase II study of temozolomide and thalidomide with radiation therapy for newly diagnosed glioblastoma multiforme. [2018]

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Temozolomide-related hematologic toxicity. [2018]

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

Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis. [2018]

9. England pubmed.ncbi.nlm.nih.gov

A Phase II Trial of Concurrent Temozolomide and Hypofractionated Stereotactic Radiotherapy for Complex Brain Metastases. [2020]