What side effects are associated with this type of intervention?

The most common treatments for Glioblastoma include Temozolomide (TMZ) and hypofractionated radiation therapy (RT). TMZ is associated with side effects such as myelosuppression, which can lead to conditions like myelodysplastic syndrome and acute myeloid leukemia, as well as liver toxicity, including cholestatic hepatitis. Hypofractionated RT can cause fatigue, skin reactions, and potential neurocognitive decline. Both treatments aim to balance efficacy with manageable toxicity, especially in elderly patients with poor performance status.

What prior FDA approvals exist?

The FDA has approved Temozolomide (TMZ) for the treatment of newly diagnosed Glioblastoma in combination with radiotherapy (RT) and as maintenance therapy. This approval is based on clinical trials demonstrating that TMZ, an oral alkylating agent, improves overall survival when used with RT. The treatment regimen often considers the methylation status of the MGMT promoter, as patients with a methylated MGMT promoter tend to respond better to TMZ. Hypofractionated RT, which involves delivering higher doses of radiation over a shorter period, is also used, particularly for elderly patients or those with poor performance status, to reduce treatment duration and associated toxicity.

What other types of research exist?

Promising novel alternatives for glioblastoma treatment in 2024 include: 1) Tumor Treating Fields (TTFields) - a non-invasive treatment that uses electric fields to disrupt cancer cell division. 2) CAR T-cell therapy - a type of immunotherapy where a patient's T cells are modified to target cancer cells. 3) Oncolytic virus therapy - using genetically modified viruses to selectively infect and kill cancer cells. 4) PARP inhibitors - targeting DNA repair mechanisms in cancer cells, particularly effective in tumors with specific genetic mutations. 5) Combination therapies - integrating immune checkpoint inhibitors (like nivolumab) with other treatments to enhance anti-tumor response.

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Chemoradiotherapy vs Biomarker-Guided Therapy for Glioblastoma

Phase 2

Recruiting

Research Sponsored by AHS Cancer Control Alberta

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Stable or decreasing dose of corticosteroids for at least 14 days prior to randomization.

Newly-diagnosed, histologically proven, intracranial glioblastoma with maximal safe resection. Biopsy alone is expected if resection is not possible. MGMT promoter methylation status must be tested for all patients.

Must not have

Unstable angina and/or congestive heart failure requiring hospitalization

Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study registration

Timeline

Screening 3 weeks

Treatment Varies

Follow Up throughout study completion, up to 5 years.

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing two treatments for elderly patients with brain cancer who are not in good health. One treatment uses a drug called Temozolomide, and the other uses a shorter course of radiation therapy. The goal is to find out if these treatments are as effective as the usual treatment but with fewer side effects.

Who is the study for?

This trial is for elderly (age ≥ 65) GBM patients with a performance status KPS of 60-70. They must have newly-diagnosed, histologically proven glioblastoma and known MGMT promoter methylation status. Participants need stable organ function and agree to use effective birth control. Exclusions include prior invasive malignancies within 3 years, recent heart issues, active hepatitis B, or severe co-morbidities.

What is being tested?

The study compares standard chemoradiotherapy (40 Gy radiation with concurrent temozolomide) against biomarker-guided therapy—either temozolomide alone for those with methylated MGMT promoters or just radiotherapy for non-methylated cases—to see which is better for survival without increasing toxicity.

What are the potential side effects?

Possible side effects include fatigue, nausea, blood disorders like low platelet/white cell counts from temozolomide; skin irritation from radiation; and potential allergic reactions to medication components.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My steroid dose has been stable or decreasing for the last 2 weeks.

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I have a new diagnosis of glioblastoma and have had surgery to remove as much as safely possible. My tumor's MGMT status is known.

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I agree not to donate sperm during and for six months after the study.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been hospitalized for heart issues recently.

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I am currently on IV antibiotics for a bacterial or fungal infection.

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I do not have any severe health issues that would prevent me from taking temozolomide.

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My brain tumor has come back after treatment.

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I haven't had radiation or systemic therapy that would interfere with temozolomide treatment.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ throughout study completion, up to 5 years.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~throughout study completion, up to 5 years.

This trial's timeline: 3 weeks for screening, Varies for treatment, and throughout study completion, up to 5 years. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall survival

Secondary study objectives

Cognitive and mental function

Cost effectiveness

Frequency of Adverse Events related to the treatment administered

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Biomarker based treatmentExperimental Treatment1 Intervention

MGMT (+) Temozolomide monotherapy: Patients will receive Temozolomide (TMZ) at a dose of 75 mg/m2 daily for 21 consecutive days. This will be followed by six cycles of TMZ according to the standard 5-day schedule (days 1-5) every 28 days. The dose will be 150 mg/m2 for the first cycle and increased to 200 mg/m2 beginning with the second cycle, so long as there are no hematologic adverse events. Dose will be determined using body surface area (BSA) calculation. MGMT methylation (-) RT monotherapy: Participants will receive radiation treatment with 40Gy / 15 fractions over a period of 21 days (3 weeks).

Group II: Standard Arm: TMZ with concurrent RT (combined modality arm)Active Control1 Intervention

Patients will receive a total of 21 days of Temozolomide (TMZ), with 15 days of TMZ administered daily with concurrent RT. TMZ will be delivered at a dose of 75 mg/m2, given daily with RT for 15 days, one hour before each session of RT. After a 4-week break, patients will receive six cycles of adjuvant TMZ according to the standard 5-day schedule (days 1-5) every 28 days, up to 6 cycles as tolerated by the patient. The dose will be 150 mg/m2 for the first cycle and increased to 200 mg/m2 beginning with the second cycle, so long as there are no hematologic adverse events, intractable nausea or fatigue.

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Temozolomide (TMZ) is an oral chemotherapy drug that works by methylating DNA, which leads to DNA damage and ultimately cell death, particularly in tumor cells with a methylated MGMT promoter, as they are less capable of repairing this damage. Hypofractionated radiation therapy (RT) involves delivering higher doses of radiation over a shorter period, targeting the tumor cells' DNA to induce damage and cell death. This approach is less taxing on elderly and frail patients compared to prolonged treatment regimens. These treatments are crucial for Glioblastoma patients as they offer a balance between efficacy and reduced toxicity, improving overall survival and quality of life.