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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy and radiation therapy to evaluate its effectiveness against certain brain tumors, specifically IDH wildtype gliomas and molecular glioblastomas. The goal is to determine if this combined treatment can better control the disease by comparing new radiation doses and methods to standard ones. This trial suits individuals diagnosed with these specific brain tumors who have not previously received chemotherapy or radiation to the head. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Previous studies have identified temozolomide as an important drug for treating brain tumors like glioblastoma. It directly attacks tumor cells. Research indicates that, when combined with other treatments, it does not significantly worsen side effects, suggesting temozolomide is generally well-tolerated.

Radiation therapy, a common treatment for brain tumors, is known for its accuracy. It targets tumor cells while sparing nearby healthy brain tissue, reducing side effects. Although radiation therapy can cause some side effects, it remains a standard treatment and is considered safe for many patients.

Together, these treatments aim to shrink the tumor and control the disease. Available data shows they are generally safe and well-tolerated when used in combination. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of temozolomide and radiation therapy for brain cancer because it offers a comprehensive approach that targets cancer cells more aggressively. Temozolomide is an oral chemotherapy drug that can enhance the effects of radiation therapy, making it a powerful duo against tumor growth. Unlike traditional methods, which often rely on either surgery or radiation alone, this combination therapy aims to maximize the destruction of cancer cells while minimizing the risk of disease progression over a longer period. This combined approach could potentially improve survival rates and quality of life for patients.

What evidence suggests that this trial's treatments could be effective for brain cancer?

Research has shown that using temozolomide with radiation therapy, as studied in this trial, can help brain cancer patients live longer. In one study, 70% of patients survived for 10 years when temozolomide was added to radiation, compared to 47% with radiation alone. Temozolomide stops tumor cells from growing and spreading, while radiation therapy uses high-energy x-rays to shrink tumors and kill cancer cells. Together, these treatments have shown promising results in controlling and reducing brain tumors. ^{2 6 7 8 9}

Who Is on the Research Team?

Debra N. Yeboa

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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

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

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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 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]

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Radiation Therapy for Glioblastoma

This heightened accuracy enables higher doses of radiation to be directed at a glioblastoma while minimizing exposure to the surrounding healthy brain tissues.