Clinical Trial - NCT03423628

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

Recruiting

Sponsor: AstraZeneca

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03423628

Protocol Info

Short Description: Phase I of AZD1390 + XRT in Combination for GBM and Brain Mets
Long Description: 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
MGH Status: Open
Sponsor: Astra Zeneca
Disease Program: Brain/CNS

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




Purpose

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
Condition Title Intervention Phase
Recurrent Glioblastoma Multiforme Primary Glioblastoma Multiforme Brain Neoplasms, Malignant Leptomeningeal Disease (LMD) Radiation Therapy AZD1390 Phase 1
Study Type Interventional
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

Primary Outcome Measures

Incidence of dose-limiting toxicities (DLTs) [Time Frame: From the start of treatment until the end of the DLT period (approximately 6 weeks for Arm A and B and 10 weeks for Arm C)] [Designated as safety issue: ]

Incidence of adverse events (AEs) and serious adverse events (SAEs) [Time Frame: From the start of treatment until the patient is off study (approximately 1 year for Arm A and C and approximately 7 weeks for Arm B)] [Designated as safety issue: ]


Secondary Outcome Measures

Event free survival (EFS) for Arms A and C only [Time Frame: From the start of treatment until the patient is off study (approximately 1 year)] [Designated as safety issue: ]

Objective response rate defined by RANO criteria for Arms A and C only [Time Frame: Every 8 weeks starting from 4 weeks after RT until the end of the study (approximately 1 year)] [Designated as safety issue: ]

Objective response rate defined by RANO-BM criteria for Arm B only [Time Frame: From screening until the patient is off study, approximately 8 weeks] [Designated as safety issue: ]

Objective response rate defined by RECIST 1.1 criteria for Arm B only [Time Frame: From screening until the patient is off study, approximately 8 weeks] [Designated as safety issue: ]

Maximum Observed Plasma Concentration (Cmax) of AZD1390 [Time Frame: At predefined intervals throughout the AZD1390 treatment period (approximately 5 weeks for Arms A and B and 9 weeks for Arm C)] [Designated as safety issue: ]

Time to observed Cmax (Tmax) for AZD1390 [Time Frame: At predefined intervals throughout the AZD1390 treatment period (approximately 5 weeks for Arms A and B and 9 weeks for Arm C)] [Designated as safety issue: ]

Area under the plasma concentration-time curve (AUC) for AZD1390 [Time Frame: At predefined intervals throughout the AZD1390 treatment period (approximately 5 weeks for Arms A and B and 9 weeks for Arm C)] [Designated as safety issue: ]

Renal clearance (CLR) for AZD1390 [Time Frame: At predefined intervals throughout the AZD1390 treatment period (approximately 5 weeks for Arms A and B and 9 weeks for Arm C)] [Designated as safety issue: ]

Estimated Enrollment: 132
Study Start Date: April 2018
Estimated Study Completion Date: April 2021
Estimated Primary Completion Date: April 2021
Arms Assigned Interventions

Experimental:AZD1390 + Radiation Therapy

AZD1390 + Radiation Therapy
Drug:AZD1390
AZD1390 Administered in 3 Cycles: Cycle 0: 1 dose prior to Radiation Therapy Cycle 1: Intermittent or continuous dosing during Radiation Therapy (except for first 2 cohorts of Arm A) Cycle 2: 2 weeks adjuvant treatment after Radiation Therapy

Eligibility

Ages Eligible for Study: 150 Years-150 Years

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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:
  • Histologically proven diagnosis of GBM. Patients who have had RT for low-grade glioma (LGG) and have subsequently relapsed to histologically confirmed GBM can be considered for inclusion in Arm A after discussion with the Medical Monitor.
  • A radiological diagnosis of recurrent/relapsed or progressive disease according to RANO criteria.
  • Completion of first-line radiation at least 6 months prior to study entry.
  • 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.
  • Non-central nervous system (CNS) malignant disease must be sufficiently controlled so that patient can be without additional systemic therapy for approximately 2 months
  • Not received radiation to the lung fields within the past 8 weeks.
  • No history of seizures related to the brain metastases or LMD.
  • Additional Inclusion Criteria Specific for Arm C:
  • Histologically proven primary diagnosis of GBM with unmethylated O6-methylguanine-DNA methyltransferase (MGMT).
  • 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

Exclusion Criteria:

  • Administration of chemotherapy or any investigational drug in the 28 days prior to receiving the first dose of treatment. 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03423628

Locations

  • United States, Massachusetts
    • Research Site Boston, Massachusetts, United States, 02114
    • Research Site Boston, Massachusetts, United States, 02215
  • United States, New York
    • Research Site New York, New York, United States, 10065
  • United States, Pennsylvania
    • Research Site Pittsburgh, Pennsylvania, United States, 15232
  • United States, Virginia
    • Research Site Richmond, Virginia, United States, 23294
  • United Kingdom,
    • Research Site Cambridge, , United Kingdom, CB2 0QQ
    • Research Site Glasgow, , United Kingdom, G12 0YN
    • Research Site Leeds, , United Kingdom,

Sponsors and Collaborators

AstraZeneca

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03423628
Other Study ID Numbers: 2017-002451-28
Study First Received:
Last Updated:
Health Authority:

Keywords provided by AstraZeneca:

glioblastoma

brain metastases

Ataxia-telangiectasia mutated kinase (ATM) inhibition

radiation therapy

Additional relevant MeSH terms:

Glioblastoma

Brain Neoplasms

Neoplasms

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019