What side effects are associated with this type of intervention?

Common treatments for Glioblastoma include radiotherapy and chemotherapy agents like temozolomide. Radiotherapy can cause side effects such as fatigue, hair loss, skin changes, and inflammation of the brain (radiation necrosis). Chemotherapy with temozolomide often leads to nausea, vomiting, loss of appetite, and myelosuppression (reduced blood cell production). Inhibitors of DNA repair mechanisms, like the ATM kinase inhibitor AZD1390, can enhance the effects of radiotherapy but may also increase the risk of side effects such as increased sensitivity to radiation, leading to more pronounced fatigue, skin reactions, and potential for more severe brain inflammation.

What prior FDA approvals exist?

The FDA has approved several treatments for Glioblastoma, including temozolomide, which is often used in combination with radiotherapy. Temozolomide works by damaging the DNA of cancer cells, thereby enhancing the effects of radiotherapy. Another relevant treatment is bevacizumab, an anti-angiogenic drug that inhibits the growth of blood vessels in tumors. While specific ATM kinase inhibitors like AZD1390 are still under investigation, these approved treatments share the common goal of enhancing radiotherapy's effectiveness by targeting cancer cell survival mechanisms.

What other types of research exist?

Promising alternatives to AZD1390 for Glioblastoma patients include ATR inhibitors like AZD6738, which has shown radiosensitization effects in multiple cancer cell lines, and PARP inhibitors, which are effective in tumors with DNA repair deficiencies. Additionally, IDH-targeted therapies such as Ivosidenib and Vorasidenib are being explored for IDH-mutant gliomas and may offer new treatment avenues.

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ATM Kinase Inhibitor

AZD1390 for Glioblastoma

Phase < 1

Recruiting

Led By Nader Sanai, MD

Research Sponsored by Nader Sanai

Eligibility Criteria Checklist

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

Must have

Be older than 18 years old

Must not have

Personal history of syncope of cardiovascular etiology, ventricular arrhythmia, or sudden cardiac arrest

Past medical history of interstitial lung disease, drug-induced ILD, or radiation pneumonitis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6 month progression-free survival (pfs6) rate measured from the time of surgery to date of recurrence.

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug, AZD1390, combined with radiation therapy in patients with severe brain cancer. AZD1390 is designed to enhance the effectiveness of radiation in killing cancer cells.

Who is the study for?

This trial is for adults over 18 with newly diagnosed or recurrent WHO Grade 4 glioma (a type of brain tumor) who are planning to have radiation. They must have measurable disease, stable seizures if present, and good organ function. Pregnant women, those with certain heart conditions or severe infections, and individuals on specific medications are excluded.

What is being tested?

The study tests AZD1390 in combination with standard radiotherapy. It includes a Phase 0 part where patients' PK response is assessed and a Phase 1b expansion for responders. The goal is to see how well AZD1390 works alongside usual cancer treatments.

What are the potential side effects?

Potential side effects of AZD1390 may include reactions related to the immune system, liver issues reflected by blood tests, possible impact on bone marrow leading to blood disorders, digestive disturbances like changes in pancreatic enzymes levels, and general symptoms such as fatigue.

Eligibility Criteria

Exclusion Criteria

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

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I have a history of fainting due to heart issues, irregular heartbeats, or sudden cardiac arrest.

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I have had lung conditions caused by drugs, disease, or radiation.

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My heart's electrical activity is normal and I don't have a long QT interval.

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I do not have any serious health conditions that would stop me from joining the study.

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I have a history of muscle disorders or high levels of muscle enzymes.

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I have previously been treated with ATM kinase inhibitors.

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I do not have any severe infections, liver disease, or active infections.

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I have a history of epilepsy or seizures not caused by a tumor.

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I am currently using a blood thinner that can't be stopped before surgery.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6 month progression-free survival (pfs6) rate measured from the time of surgery to date of recurrence.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6 month progression-free survival (pfs6) rate measured from the time of surgery to date of recurrence.

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 month progression-free survival (pfs6) rate measured from the time of surgery to date of recurrence. for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Phase 0: The relative pharmacokinetics (PK) of AZD1390 in tumor tissue from Grade 4 glioma participants treated with AZD1390

Phase 1b: Examine the rate of 6-month progression-free survival glioma participants with demonstrated PK effect.

Secondary study objectives

Adverse events

Deaths

Drug-related toxicity

+3 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: Arm C: Newly-diagnosed Grade 4 GliomaExperimental Treatment1 Intervention

Group II: Arm B: Recurrent Grade 4 Glioma Dose EscalationExperimental Treatment1 Intervention

Group III: Arm A: Recurrent Grade 4 Glioma Surgical Cohort Time EscalationExperimental Treatment1 Intervention

0 / 9Eligibility 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

Common treatments for Glioblastoma include radiotherapy and chemotherapy. Radiotherapy damages the DNA of cancer cells, leading to cell death, but its effectiveness is often limited by the cancer cells' ability to repair this damage. Agents like AZD1390, an ATM kinase inhibitor, enhance the effects of radiotherapy by preventing DNA repair in cancer cells. This mechanism is significant for Glioblastoma patients as it can potentially improve the efficacy of standard treatments, leading to better clinical outcomes and prolonged survival.