RECRUITING

A Study to Assess the Safety and Tolerability of AZD1390 Given With Radiation Therapy in Patients With Brain Cancer

Conditions

Recurrent Glioblastoma Multiforme Primary Glioblastoma Multiforme Brain Neoplasms, Malignant Leptomeningeal Disease (LMD)glioblastoma Ataxia-telangiectasia mutated kinase (ATM) inhibition radiation therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study will test an investigational drug called AZD1390 in combination with radiation therapy for the treatment of brain tumors. This is the first time AZD1390 is being given to patients. This study will test safety, tolerability and PK (how the drug is absorbed, distributed and eliminated) of ascending doses of AZD1390 in combination with distinct regimens of radiation therapy

Official Title

A Phase I, Multicentre 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.

Quick Facts

Study Start:2018-04-02

Study Completion:2026-09-16

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03423628

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 130 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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: * 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.	* 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 * Diabetes Type I, Type II, or steroid-induced diabetes. * Undergoing systemic steroid treatment \Note: the optional food effect assessment is currently not open to enrolment\

Inclusion Criteria

Exclusion 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:
* 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.

* 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
* Diabetes Type I, Type II, or steroid-induced diabetes.
* Undergoing systemic steroid treatment \*Note: the optional food effect assessment is currently not open to enrolment\*

Contacts and Locations

Study Contact

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479

information.center@astrazeneca.com

Principal Investigator

Patrick Wen

PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Brandon Imber

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Mariza Daras

PRINCIPAL_INVESTIGATOR

VCU Massey Cancer Center

Jan Drappatz

PRINCIPAL_INVESTIGATOR

UPMC Hospital Radiation Oncology

Deborah Forst

PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Anthony Chalmers

PRINCIPAL_INVESTIGATOR

Beatson West of Scotland Cancer Centre

Rajesh Jena

PRINCIPAL_INVESTIGATOR

Cambridge University Hospitals NHS Foundation Trust

Susan Short

PRINCIPAL_INVESTIGATOR

University of Leeds

Study Locations (Sites)

Research Site

Boston, Massachusetts, 02114

United States

Research Site

Boston, Massachusetts, 02215

United States

Research Site

New York, New York, 10065

United States

Research Site

Pittsburgh, Pennsylvania, 15232

United States

Research Site

Richmond, Virginia, 23298

United States

Collaborators and Investigators

Sponsor: AstraZeneca

Patrick Wen, PRINCIPAL_INVESTIGATOR, Dana-Farber Cancer Institute
Brandon Imber, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center
Mariza Daras, PRINCIPAL_INVESTIGATOR, VCU Massey Cancer Center
Jan Drappatz, PRINCIPAL_INVESTIGATOR, UPMC Hospital Radiation Oncology
Deborah Forst, PRINCIPAL_INVESTIGATOR, Massachusetts General Hospital
Anthony Chalmers, PRINCIPAL_INVESTIGATOR, Beatson West of Scotland Cancer Centre
Rajesh Jena, PRINCIPAL_INVESTIGATOR, Cambridge University Hospitals NHS Foundation Trust
Susan Short, PRINCIPAL_INVESTIGATOR, University of Leeds

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2018-04-02

Study Completion Date2026-09-16

Study Record Updates

Study Start Date2018-04-02

Study Completion Date2026-09-16

Terms related to this study

Keywords Provided by Researchers

glioblastoma
Ataxia-telangiectasia mutated kinase (ATM) inhibition
radiation therapy

Additional Relevant MeSH Terms

Recurrent Glioblastoma Multiforme
Primary Glioblastoma Multiforme
Brain Neoplasms, Malignant
Leptomeningeal Disease (LMD)