What side effects are associated with this type of intervention?

Common treatments for glioblastoma, such as radiation therapy and temozolomide chemotherapy, have several known side effects. Radiation therapy can cause fatigue, hair loss, skin irritation at the treatment site, and potential cognitive decline due to brain tissue damage. Temozolomide chemotherapy is associated with side effects like nausea, vomiting, loss of appetite, constipation, fatigue, and myelosuppression, which can lead to increased risk of infection, anemia, and bleeding. When higher doses of radiation are targeted to the subventricular zone, there may be an increased risk of neurotoxicity and cognitive impairment.

What prior FDA approvals exist?

The FDA has approved several treatments for Glioblastoma, focusing on a combination of radiation therapy and chemotherapy. Temozolomide (Temodar) is a key FDA-approved drug used in conjunction with radiation therapy for newly diagnosed Glioblastoma. This regimen involves daily temozolomide during radiation therapy, followed by monthly maintenance doses. Additionally, bevacizumab (Avastin) has been approved for recurrent Glioblastoma, primarily for its anti-angiogenic properties. These treatments aim to improve survival and manage symptoms, similar to the goals of the modified radiation therapy being studied.

What other types of research exist?

Promising novel alternatives to modified radiation therapy for glioblastoma patients in 2024 include: 1) Immunotherapy, such as checkpoint inhibitors (e.g., nivolumab) and CAR-T cell therapy, which harness the immune system to target cancer cells. 2) Targeted therapies, including agents targeting specific mutations (e.g., EGFR inhibitors) and pathways involved in glioblastoma growth. 3) Advanced local treatments like laser interstitial thermal therapy (LITT) and brachytherapy, which deliver precise, high-dose radiation to tumors while sparing surrounding tissue. 4) Combination therapies that integrate systemic treatments with localized approaches to enhance overall efficacy.

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SVZ Radiation + Temozolomide for Glioblastoma

Phase 2

Recruiting

Led By Kristin Redmond, M.D.

Research Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria Checklist

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

Must have

ECOG performance status 0-2 (Karnofsky >60%).

Patient must be scheduled to receive temozolomide concurrent with and following radiation.

Must not have

Use of Avastin or another VEG-F inhibitor prior to progression is not permitted.

Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and up to 12 weeks after the study are excluded.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up one year post completion of radiation treatment

Awards & highlights

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial tests if giving extra radiation to a specific brain area along with standard cancer treatment can help control glioblastoma for a longer time in newly diagnosed patients. The treatment for newly diagnosed glioblastoma changed when radiation therapy plus temozolomide chemotherapy replaced radiation therapy alone.

Who is the study for?

This trial is for adults with newly diagnosed Glioblastoma Multiforme (GBM) who've had surgery but no brain radiation before. They must start treatment within 12 weeks of surgery, have a performance status allowing daily activities with effort or better, and agree to use contraception. Pregnant women, those unwilling to prevent pregnancy, and patients with other serious illnesses or prior cancers (except certain skin cancers and treated cervical cancer) are excluded.

What is being tested?

The study tests if targeting the subventricular zone (SVZ)—a brain area containing stem cells—with higher-dose radiation alongside standard chemotherapy (Temozolomide), can control GBM longer than standard therapy alone. Patients will receive this modified radiation plan over six weeks to see if it improves outcomes.

What are the potential side effects?

Potential side effects include typical reactions from radiation such as fatigue, hair loss at the treatment site, headaches, nausea; and from Temozolomide like nausea, vomiting, constipation, loss of appetite and risk of infections due to lowered blood cell counts.

Eligibility Criteria

Inclusion Criteria

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

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I can care for myself and am up more than 50% of my waking hours.

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I am scheduled for treatment with temozolomide alongside and after radiation.

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I have been recently diagnosed with glioblastoma.

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I have never had radiation therapy to my brain.

Exclusion Criteria

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

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I have not used Avastin or any VEG-F inhibitor before my cancer progressed.

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I am not pregnant or breastfeeding and will use birth control during and up to 12 weeks after the study.

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I do not have any severe illnesses that could interfere with the study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ one year post completion of radiation treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~one year post completion of radiation treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and one year post completion of radiation treatment for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Change from Baseline to Initial Progression

Secondary study objectives

Acute and Late Toxicity Change from Baseline

Cognitive Function Change from Baseline

Composite Cognitive Function Change from Baseline

+9 more

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

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: Temozolomide plus radiation therapy to the tumor and SVZExperimental Treatment2 Interventions

Patients will be scheduled to receive continuous daily temozolomide (75 mg per square meter of body surface area per day, 7 days per week from the first to the last day of radiation therapy), followed by 6 cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle). Patients will receive 60 Gy of radiation therapy in 30 fractions, 5 days per week using IMRT. The target delineation and treatment volumes will be as follows: Initial treatment plan will include the tumor bed and MRI changes based on T1 post gadolinium series and FLAIR series, plus the bilateral subventricular zone Will be prescribed to 46 Gy in 2 Gy fractions Cone down treatment plan will include the tumor bed, areas of contrast enhancement on T1 post gadolinium series MRI plus the ipsilateral subventricular zone Will be prescribed to 14 Gy in 2 Gy fractions

Group II: Temozolomide and neural progenitor cell sparing radiationActive Control2 Interventions

Patients will receive continuous daily temozolomide (75 mg per square meter of body surface area per day, 7 days per week from the first to the last day of radiation therapy), followed by 6 cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle). Patients will receive 60 Gy in 30 fractions, 5 days per week using IMRT. The target delineation and treatment volumes will be as follows: Initial treatment plan will include the tumor bed and MRI abnormalities based on T1 post gadolinium series and FLAIR series. Will be prescribed to 46 Gy in 2 Gy fractions Cone down treatment plan will include the tumor bed and MRI changes based on T1 post gadolinium series. Will be prescribed to 14 Gy in 2 Gy fractions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Temozolomide

FDA approved

0 / 7Eligibility 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

Glioblastoma treatment commonly involves a combination of radiation therapy and temozolomide chemotherapy. Radiation therapy works by damaging the DNA of cancer cells, which inhibits their ability to replicate and leads to cell death. This is crucial for controlling tumor growth and reducing the tumor burden. Temozolomide is an oral chemotherapy drug that also targets cancer cell DNA, causing breaks that prevent the cells from dividing. This dual approach is significant for Glioblastoma patients because it maximizes the potential to control the aggressive and rapidly growing nature of the tumor. The trial studying modified radiation therapy aims to deliver a higher dose to the subventricular zone, an area believed to harbor cancer stem cells, potentially reducing recurrence and improving long-term outcomes.