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Assessing AZD1390 with Radiation Therapy for Brain Cancer

A Phase I, Multicenter Study to Assess the Safety, Tolerability, and Pharmacokinetics of Ascending Doses of AZD1390 in Combination With Radiation Therapy in Patients With Glioblastoma Multiforme and Brain Metastases From Solid Tumors

Phase 1 Interventional AstraZeneca · NCT03423628

This study is testing a new drug called AZD1390 combined with radiation therapy to see if it is safe and effective for people with brain tumors like glioblastoma.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment180 (estimated)
Ages18 Years to 130 Years
SexAll
SponsorAstraZeneca Industry-sponsored
Drugs / interventionschemotherapy, radiation
Locations12 sites (Boston, Massachusetts and 11 other locations)
Trial IDNCT03423628 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and tolerability of an investigational drug, AZD1390, in combination with radiation therapy for patients with brain tumors, specifically recurrent and primary glioblastoma multiforme. It is a Phase 1, open-label, multicenter study conducted in the United States, the United Kingdom, and Japan, featuring three treatment arms with varying radiation regimens. The study aims to determine how well AZD1390 is absorbed, distributed, and eliminated in the body while assessing its safety in conjunction with standard radiation treatments.

Who should consider this trial

Good fit: Ideal candidates include patients with histologically confirmed recurrent or primary glioblastoma multiforme who have completed first-line radiation therapy at least six months prior.

Not a fit: Patients with low-grade gliomas or those who have not had prior radiation therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new therapeutic option for patients with aggressive brain tumors, potentially improving treatment outcomes.

How similar studies have performed: While this approach is novel in the context of AZD1390, similar studies combining targeted therapies with radiation have shown promise in treating brain tumors.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Provision of formalin-fixed paraffin embedded tissue sample from primary or metastatic disease
* Karnofsky Performance Score of ≥60.
* Additional Inclusion Criteria Specific for Arm A and Japan:

  * Histologically proven diagnosis of GBM. Patients who have had RT for low-grade glioma (LGG) or grade 3 glioma and have subsequently relapsed to histologically confirmed GBM can be considered
  * A radiological diagnosis of recurrent/relapsed or progressive disease according to RANO criteria.
  * Completion of first-line radiation at least 6 months prior to Cycle 1 Day 1.
  * Patients with tumor-induced seizures must be well controlled on a stable anti-epileptic treatment
  * Willing to receive anti-epileptic prophylaxis for the duration of study drug administration.
* Additional Inclusion Criteria Specific for Arm B:

\*\*Arm B has now closed to recruitment\*\*

* Histologically proven diagnosis of solid tumor malignancy and Magnetic Resonance (MR) imaging documenting brain lesions.
* Not eligible for Stereotactic Radiosurgery (SRS) treatment of brain tumor.
* Patient has not received any previous brain RT to the area that is to be irradiated. Prior PBRT may be allowed if there is not significant overlap between the prior and new radiation fields.
* Non-CNS malignant disease must be sufficiently controlled so that patients can be without additional systemic therapy for the required washout period before starting therapy until 5 days after the end of RT. Required washout period before starting the first dose of AZD1390 (Cycle 1) is 28 days for immune checkpoint inhibitors and 7 days for all other agents
* Not received radiation to the lung fields within the past 8 weeks.
* No history of seizures related to the brain metastases or LMD.
* Receiving PBRT (rather than WBRT) during Cycle 1 as standard of care for brain metastases

  • Additional Inclusion Criteria Specific for Arm C:
* Histologically proven primary diagnosis of GBM with unmethylated O6-methylguanine-DNA methyltransferase (MGMT). Grade 4 astrocytoma or histology with molecular features of GBM can be considered.
* Determination of MGMT promoter status by methylation-specific polymerase chain reaction (PCR) or pyrosequencing per local institutional guidelines is required to assess eligibility for this Arm.
* Patients will have to undergo mutational testing for Isocitrate dehydrogenase 1 (IDH1) on a tumor specimen before entering study. Patients are eligible for Arm C regardless of their IDH1 mutational status.
* No history of uncontrolled seizures after surgery for primary GBM (despite adequate antiepileptic therapy) or with need for concurrent administration of more than 2 antiepileptic drugs.
* Willing to receive anti-epileptic prophylaxis for the duration of study drug administration

Additional Inclusion criteria for Food Effect Assessment (Arm A):

* For the fed assessment portion: fast overnight (for at least 10 hours) prior to consuming a high-fat meal consisting of approximately 800 to 1000 calories, with around 54% of the calories coming from fat.
* For the fasted assessment portion: fast overnight (for at least 10 hours prior to dosing) and until 4 hours after dosing.

\*Note: the optional food effect assessment is currently open to enrolment\*

Exclusion Criteria:

* Administration of chemotherapy or any investigational drug in the 28 days or carmustine (CCNU) or lomustine (BCNU) in the 6 weeks prior to receiving the first dose of treatment in Arms A and C. Administration of checkpoint inhibitors within 28 days prior to first dose of treatment and any other agent within 7 days of beginning study treatment in Arm B. Hormonal therapies are allowed during study treatment for patients in Arm B.
* History of severe brain-injury or stroke.
* Patient not eligible for sequential MRI evaluations are not eligible for this study.
* History of epileptic disorder or any seizure history unrelated to tumor
* Treatment with Strong inhibitors or inducers of CYP3A4 within 2 weeks prior to receiving study drug
* Concurrent therapy with other seizurogenic medications.
* Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
* Concurrent severe and/or uncontrolled medical condition (e.g., severe COPD).
* Prior treatment with pneumotoxic drugs, e.g. busulfan, bleomycin, within the past year. If prior therapy in lifetime, then excluded if history of pulmonary toxicities from administration. Patients who have received treatment with nitrosoureas (e.g., carmustine, lomustine) in the year before study entry without experiencing lung toxicity are allowed on study.
* History or presence of myopathy or raised creatine kinase (CK) \>5 x upper limit of normal (ULN) on 2 occasions at screening.
* Cardiac dysfunction defined as: Myocardial infarction within six months of study entry, NYHA (New York Heart Association) Class II/III/IV heart failure, unstable angina, unstable cardiac arrhythmias
* Evidence of severe pulmonary infections, as judged by the investigator (For Japan part only this includes active infection including tuberculosis, chronic active or uncontrolled Hep B or Hep C)
* With the exception of alopecia, any unresolved toxicities from prior therapy greater than National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 4.03) Grade 1 at the time of starting study treatment and patients with chronic Grade 2 unresolved toxicities may be eligible Additional exclusion criteria for Arm A and Japan Part
* Has previously received ATM inhibitor with concurrent RT

Additional Exclusion criteria for Food Effect Assessment (Arm A) (Not applicable for the Japan Part):

* Diabetes Type I, Type II, or steroid-induced diabetes.
* Undergoing systemic steroid treatment \*Note: the food effect assessment is currently open to enrolment\*

Where this trial is running

Boston, Massachusetts and 11 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Recurrent Glioblastoma MultiformePrimary Glioblastoma MultiformeBrain Neoplasms, MalignantLeptomeningeal DiseaseglioblastomaAtaxia-telangiectasia mutated kinase inhibitionradiation therapy
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.