97 Participants Needed

AZD1390 for Glioblastoma

P0
Overseen ByPhase 0 Navigator
Age: 18+
Sex: Any
Trial Phase: Phase < 1
Sponsor: Nader Sanai
Must be taking: Levetiracetam
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that you cannot use certain medications like coumarin-derived anticoagulants and strong inhibitors or inducers of CYP3A4. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the drug AZD1390 for glioblastoma?

Research shows that AZD1390 can reach effective concentrations in brain tumor areas, even though its distribution in the brain is limited by certain proteins. This suggests it could enhance the effects of radiation therapy in treating glioblastoma.12345

What makes the drug AZD1390 unique for treating glioblastoma?

AZD1390 is unique because it inhibits the ataxia-telangiectasia mutated kinase, a key regulator of the DNA damage response, which can enhance the effectiveness of radiation therapy in treating glioblastoma. Despite challenges in crossing the blood-brain barrier, it achieves effective concentrations in tumor areas, making it a promising option for radiosensitization in brain tumors.12367

What is the purpose of this trial?

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.

Research Team

NS

Nader Sanai, MD

Principal Investigator

Chief Scientific Officer/Director

Eligibility Criteria

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.

Inclusion Criteria

My blood tests show my organs and bone marrow are working well.
I can take pills by mouth.
For females of reproductive potential: use of highly effective contraception and agreement to use such a method during study participation
See 10 more

Exclusion Criteria

I have risk factors for abnormal heart rhythms.
Known allergic reactions to components of the AZD1390
I have a history of fainting due to heart issues, irregular heartbeats, or sudden cardiac arrest.
See 13 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 0

Participants undergo pharmacokinetic analysis of AZD1390 in tumor tissue

Intraoperative
1 visit (in-person)

Phase 1b Expansion

Participants receive therapeutic dosing of AZD1390 plus standard-of-care fractionated radiotherapy

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months
Every 3 months

Treatment Details

Interventions

  • AZD1390
Trial Overview 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.
Participant Groups
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

Find a Clinic Near You

Who Is Running the Clinical Trial?

Nader Sanai

Lead Sponsor

Trials
11
Recruited
440+

AstraZeneca

Industry Sponsor

Trials
4,491
Recruited
290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Ivy Brain Tumor Center

Collaborator

Trials
12
Recruited
910+

Barrow Neurological Institute

Collaborator

Trials
27
Recruited
7,100+

Findings from Research

Temozolomide (TMZ) and the checkpoint kinase inhibitor AZD7762 both showed time- and concentration-dependent cytotoxic effects on human glioma cells, with their combination resulting in synergistic effects that enhance cell death.
The combination treatment of TMZ and AZD7762 not only suppressed the expression of the DNA repair protein MGMT but also modulated several signaling pathways, suggesting a complex mechanism that may improve the efficacy of glioma treatment.
Temozolomide and AZD7762 Induce Synergistic Cytotoxicity Effects on Human Glioma Cells.Chen, Y., Tseng, BJ., Tsai, YH., et al.[2022]
AZD1775 demonstrated effective penetration across the blood-brain barrier in glioblastoma patients, with a tumor-to-plasma concentration ratio indicating significant drug accumulation in tumors.
The study revealed that the acidic environment of tumors enhances AZD1775 uptake via specific transporters, while factors like blood-brain barrier integrity and transporter activity contribute to variability in drug penetration.
Quantitative and Mechanistic Understanding of AZD1775 Penetration across Human Blood-Brain Barrier in Glioblastoma Patients Using an IVIVE-PBPK Modeling Approach.Li, J., Wu, J., Bao, X., et al.[2019]

References

The third-generation EGFR inhibitor AZD9291 overcomes primary resistance by continuously blocking ERK signaling in glioblastoma. [2022]
The mTORC1/mTORC2 inhibitor AZD2014 enhances the radiosensitivity of glioblastoma stem-like cells. [2021]
Central Nervous System Distribution of the Ataxia-Telangiectasia Mutated Kinase Inhibitor AZD1390: Implications for the Treatment of Brain Tumors. [2023]
Dual mTORC1/2 blockade inhibits glioblastoma brain tumor initiating cells in vitro and in vivo and synergizes with temozolomide to increase orthotopic xenograft survival. [2021]
Temozolomide and AZD7762 Induce Synergistic Cytotoxicity Effects on Human Glioma Cells. [2022]
Biological characteristics of a new human glioma cell line transformed into A2B5(+) stem cells. [2021]
Quantitative and Mechanistic Understanding of AZD1775 Penetration across Human Blood-Brain Barrier in Glioblastoma Patients Using an IVIVE-PBPK Modeling Approach. [2019]
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