A Study to Assess the Safety and Tolerability of AZD1390 Given With Radiation Therapy in Patients With Brain Cancer
NCT ID: NCT03423628
Last Updated: 2025-11-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1
180 participants
INTERVENTIONAL
2018-04-02
2026-09-16
Brief Summary
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Detailed Description
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* Arm A: 35 Gy over 2 weeks with intensity-modulated radiation therapy (IMRT) in patients with recurrent Glioblastoma Multiforme (GBM). Arm A will also include the food effect cohort
* Arms B: 30 Gy over two weeks with whole brain radiation therapy (WBRT)/ partial brain radiation therapy (PBRT) in patients with brain metastases. \*\*Arm B has now closed to recruitment\*\*
* Arm C: 60 Gy over 6 weeks (IMRT) in patients with primary GBM Each arm provides standard of care RT for the disease setting indicated with the experimental agent being administered in dose escalating cohorts.
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
In arms A and C, AZD1390 will be administered in three cycles: Cycle 0 (before RT), Cycle 1 (during RT) and Cycle 2 (after RT).
In arm B, AZD1390 will be administered in cycle 1 only (during RT). Within each arm, AZD1390 will be administered in dose escalating cohorts, first in an intermittent and then in a consecutive fashion, to achieve daily administration prior to RT.
\*\*Arm B has now closed to recruitment\*\*
For Arm A, there is an optional food effect assessment during cycle 0. \*Note: the food effect assessment is currently open to recruitment\*
TREATMENT
NONE
Study Groups
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Arm A: AZD1390 + Radiation Therapy
AZD1390 administration plus 35 Gy of Intensity-modulated radiation therapy (IMRT) administered at daily fractions of 3.5 Gy over 10 fractions (2 weeks)
AZD1390
AZD1390 Administered in 3 Cycles depending on arm:
Cycle 0: 1 dose prior to Radiation Therapy. Cycle 1: 2 weeks Intermittent or continuous dosing during Radiation Therapy. Cycle 2: 2 weeks adjuvant treatment after Radiation Therapy. For optional food effect assessment in Arm A, 2 doses prior to RT under both fed and fasted conditions. Note: the food effect assessment is currently open to recruitment.
Arm A includes the Japan part following the same dosing administration.
Radiation Therapy
35 Gy of Intensity-modulated radiation therapy (IMRT) administered at daily fractions of 3.5 Gy over 10 fractions (2 weeks)
Arm B: AZD1390 + Radiation Therapy
AZD1390 administration plus 30 Gy of whole brain radiation therapy (WBRT) or partial brain radiation therapy (PBRT) administered at daily fractions of 3 Gy over 10 fractions (2 weeks).
Radiation Therapy
30 Gy of whole brain radiation therapy (WBRT) or partial brain radiation therapy (PBRT) administered at daily fractions of 3 Gy over 10 fractions (2 weeks).
AZD1390
AZD1390 administered in 1 Cycle. AZD1390 administration concomitantly with RT (2 weeks). Cycle 1 also contains an additional 5 days (post completion of RT with AZD1390 administration). Arm is Closed.
Arm C: AZD1390 + Radiation Therapy
AZD1390 administration plus 60 Gy of intensity- modulated radiation therapy (IMRT) administered at daily fractions of 2 Gy over 30 fractions (6 weeks)
Radiation Therapy
60 Gy of intensity- modulated radiation therapy (IMRT) administered at daily fractions of 2 Gy over 30 fractions (6 weeks)
AZD1390
AZD1390 Administered in 3 Cycles depending on arm:
Cycle 0: 1 dose prior to Radiation Therapy. Cycle 1: 6 weeks Intermittent or continuous dosing during Radiation Therapy. Cycle 2: 2 weeks adjuvant treatment after Radiation Therapy. Arm is closed.
Interventions
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AZD1390
AZD1390 Administered in 3 Cycles depending on arm:
Cycle 0: 1 dose prior to Radiation Therapy. Cycle 1: 2 weeks Intermittent or continuous dosing during Radiation Therapy. Cycle 2: 2 weeks adjuvant treatment after Radiation Therapy. For optional food effect assessment in Arm A, 2 doses prior to RT under both fed and fasted conditions. Note: the food effect assessment is currently open to recruitment.
Arm A includes the Japan part following the same dosing administration.
Radiation Therapy
30 Gy of whole brain radiation therapy (WBRT) or partial brain radiation therapy (PBRT) administered at daily fractions of 3 Gy over 10 fractions (2 weeks).
Radiation Therapy
60 Gy of intensity- modulated radiation therapy (IMRT) administered at daily fractions of 2 Gy over 30 fractions (6 weeks)
AZD1390
AZD1390 administered in 1 Cycle. AZD1390 administration concomitantly with RT (2 weeks). Cycle 1 also contains an additional 5 days (post completion of RT with AZD1390 administration). Arm is Closed.
AZD1390
AZD1390 Administered in 3 Cycles depending on arm:
Cycle 0: 1 dose prior to Radiation Therapy. Cycle 1: 6 weeks Intermittent or continuous dosing during Radiation Therapy. Cycle 2: 2 weeks adjuvant treatment after Radiation Therapy. Arm is closed.
Radiation Therapy
35 Gy of Intensity-modulated radiation therapy (IMRT) administered at daily fractions of 3.5 Gy over 10 fractions (2 weeks)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Karnofsky Performance Score of ≥60.
* 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.
\*\*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
* 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
* 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
* 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)
* Has previously received ATM inhibitor with concurrent RT
* Diabetes Type I, Type II, or steroid-induced diabetes.
* Undergoing systemic steroid treatment \*Note: the food effect assessment is currently open to enrolment\*
18 Years
130 Years
ALL
No
Sponsors
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AstraZeneca
INDUSTRY
Responsible Party
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Principal Investigators
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Patrick Wen
Role: PRINCIPAL_INVESTIGATOR
Dana-Farber Cancer Institute
Brandon Imber
Role: PRINCIPAL_INVESTIGATOR
Memorial Sloan Kettering Cancer Center
Mariza Daras
Role: PRINCIPAL_INVESTIGATOR
VCU Massey Cancer Center
Jan Drappatz
Role: PRINCIPAL_INVESTIGATOR
UPMC Hospital Radiation Oncology
Deborah Forst
Role: PRINCIPAL_INVESTIGATOR
Massachusetts General Hospital
Anthony Chalmers
Role: PRINCIPAL_INVESTIGATOR
Beatson West of Scotland Cancer Centre
Rajesh Jena
Role: PRINCIPAL_INVESTIGATOR
Cambridge University Hospitals NHS Foundation Trust
Louise Murray
Role: PRINCIPAL_INVESTIGATOR
University of Leeds
Yoshitaka Narita
Role: PRINCIPAL_INVESTIGATOR
National Cancer Center Hospital
Yoshiki Arakawa
Role: PRINCIPAL_INVESTIGATOR
Kyoto University Hospital
Kazuhiko Mishima
Role: PRINCIPAL_INVESTIGATOR
Saitama Medical University International Medical Center
Locations
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Research Site
Boston, Massachusetts, United States
Research Site
Boston, Massachusetts, United States
Research Site
New York, New York, United States
Research Site
Pittsburgh, Pennsylvania, United States
Research Site
Richmond, Virginia, United States
Research Site
Chūōku, , Japan
Research Site
Hidaka-shi, , Japan
Research Site
Kyoto, , Japan
Research Site
Cambridge, , United Kingdom
Research Site
Glasgow, , United Kingdom
Research Site
Leeds, , United Kingdom
Research Site
London, , United Kingdom
Countries
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Central Contacts
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AstraZeneca Clinical Study Information Center
Role: CONTACT
Phone: 1-877-240-9479
Email: [email protected]
Other Identifiers
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135803
Identifier Type: REGISTRY
Identifier Source: secondary_id
2017-002451-28
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
D6940C00002
Identifier Type: -
Identifier Source: org_study_id