What side effects are associated with this type of intervention?

Common treatments for glioblastoma include radiation therapy, temozolomide, and enzyme inhibitors like adavosertib. Radiation therapy can cause side effects such as fatigue, hair loss, and skin changes. Temozolomide, a chemotherapy drug, often leads to nausea, vomiting, fatigue, and increased risk of infection due to lowered blood cell counts. Adavosertib, an enzyme inhibitor, may cause side effects including diarrhea, nausea, fatigue, and hematologic abnormalities. Combining these treatments may enhance efficacy but also increase the likelihood and severity of side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for glioblastoma, focusing on different mechanisms of action. Temozolomide, an oral alkylating agent, is commonly used in combination with radiation therapy. Bevacizumab, an anti-angiogenic drug, targets vascular endothelial growth factor (VEGF) to inhibit tumor blood vessel growth. While Adavosertib, a Wee1 kinase inhibitor, is being studied for its potential to enhance the effects of radiation and temozolomide by blocking enzymes needed for cell growth, it has not yet received FDA approval. Other enzyme inhibitors like buparlisib have been explored but faced challenges in safety and efficacy, leading to discontinued development.

What other types of research exist?

Promising alternatives to Adavosertib for glioblastoma treatment include: 1) Tumor Treating Fields (TTF) - a novel, non-invasive treatment modality 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 glioblastoma cells. 3) Oncolytic virus therapy - using genetically modified viruses to selectively infect and kill cancer cells. 4) Pembrolizumab - an immune checkpoint inhibitor that has shown promise in treating glioblastoma. 5) Bevacizumab - an anti-angiogenic agent that inhibits the growth of blood vessels in tumors.

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ATR Kinase Inhibitor

Adavosertib + Radiation + Temozolomide for Glioblastoma

Phase 1

Waitlist Available

Led By Eudocia Q Lee

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

Patients must have a tumor tissue form indicating availability of archived tissue from initial resection at diagnosis of glioblastoma completed and signed by a pathologist

Patients must have a Karnofsky performance status >= 60%

Must not have

Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol

Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or AZD1775 (adavosertib) are ineligible

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the safety and best dose of adavosertib combined with radiation and temozolomide for treating glioblastoma. Adavosertib blocks enzymes needed for tumor growth, while radiation and temozolomide kill cancer cells and stop them from growing. The study aims to find the most effective dose and understand how well this combination works for patients with newly diagnosed or recurrent glioblastoma.

Who is the study for?

This trial is for adults with new or recurrent glioblastoma who can provide tissue samples, have a decent performance status (able to care for themselves), normal organ and marrow function, no severe allergies to similar drugs, and not on certain medications. Women must test negative for pregnancy and agree to birth control.

What is being tested?

The trial tests the combination of adavosertib with radiation therapy and temozolomide chemotherapy in patients with glioblastoma. It aims to find the best dose of adavosertib that's effective when used alongside standard treatments without causing severe side effects.

What are the potential side effects?

Potential side effects include issues related to cell growth inhibition which may affect various organs, typical chemotherapy-related symptoms like nausea, fatigue, hair loss, blood disorders as well as risks associated with radiation such as skin irritation at the treatment site.

Eligibility Criteria

Inclusion Criteria

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

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I have a signed form proving I have tissue from my initial brain tumor surgery.

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I can care for myself but may need occasional help.

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I have no other cancers except possibly treated skin, cervical, breast, or bladder cancer.

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I can swallow pills without any issues.

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I have been diagnosed with glioblastoma.

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My glioblastoma has returned or worsened after radiation and possibly chemotherapy.

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I am scheduled for a surgery that my doctors say I need.

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My kidney function is within the normal range.

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I am not pregnant and agree to use two forms of birth control or abstain.

Exclusion Criteria

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

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I am not taking any medication for epilepsy that increases enzyme activity.

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I have no allergies to temozolomide or similar drugs.

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I am not HIV-positive or not on antiretroviral therapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 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

Incidence of toxicities

Maximum tolerated dose of adavosertib with 6 weeks of radiotherapy and temozolomide (Arm I)

Temozolomide

Secondary study objectives

Overall survival

Progression-free survival

Other study objectives

Apoptosis (cleaved caspase 3) levels

Genotyping data

Intratumoral adavosertib concentration

+8 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

Group I: Arm II (adavosertib, temozolomide)Experimental Treatment2 Interventions

Patients receive adavosertib PO QD on days 1, 3, and 5 or 1-5 weekly, and temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (adavosertib, temozolomide, radiation)Experimental Treatment3 Interventions

INITIATION CYCLE: Patients receive adavosertib PO on days 1, 3, and 5 or 1-5 weekly and temozolomide PO QD for 6 weeks. Patients also undergo concurrent radiation therapy 5 days per week for 6 weeks. MAINTENANCE CYCLES: Beginning in week 10, patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Temozolomide

2010

Completed Phase 3

~1880

Adavosertib

2015

Completed Phase 2

~570

Radiation Therapy

2017

Completed Phase 3

~7250

0 / 12Eligibility 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 treatments often involve a combination of therapies to target tumor cells effectively. Adavosertib is an enzyme inhibitor that blocks specific enzymes needed for tumor cell growth, potentially halting tumor progression. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors, directly damaging the DNA of cancer cells. Temozolomide is a chemotherapy drug that interferes with the DNA replication process in tumor cells, preventing them from dividing and spreading. These treatments are crucial for Glioblastoma patients as they work synergistically to target the tumor through different mechanisms, potentially improving treatment outcomes and survival rates.