AZD1390 in Recurrent and Newly Diagnosed WHO Grade 4 Glioma Patients

NCT05182905 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: Ivy 2020-10
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-center Phase 0/1b study that will enroll at least 27 participants with recurrent WHO Grade 4 Glioma requiring re-radiation and approximately 35 participants with newly-diagnosed WHO Grade 4 glioma (nGBM). The trial will be composed of a Phase 0 component (subdivided into Arms A - C), and an expansion Phase 1b. Patients with tumors demonstrating a positive PK response in the Phase 0 component of the study will be eligible to graduate to an expansion phase that combines therapeutic dosing of AZD1390 plus standard-of-care fractionated radiotherapy (RT).

Conditions

Glioblastoma; Glioma; Glioblastoma Multiforme; Glioma, Malignant

Outcome Measures

Primary Outcomes (2)

• Phase 0: The relative pharmacokinetics (PK) of AZD1390 in tumor tissue from Grade 4 glioma participants treated with AZD1390

  For PK analysis, total and unbound AZD1390 concentration in Gd-enhancing and Gd-non-enhancing tumor tissue.

  Phase 0 Intraoperative

• Phase 1b: Examine the rate of 6-month progression-free survival glioma participants with demonstrated PK effect.

  The rate of 6-month progression-free survival (PFS6) measured from time of surgery to date of recurrence or death, whichever occurs first, will be summarized.

  From the date of Phase 0 surgery to the date of progression

Secondary Outcomes (6)

• Phase 0: To evaluate the relative pharmacokinetics (PK) of AZD1390 in CSF

  Phase 0 Intraoperative

• Drug-related toxicity

  Through study completion, an average of once a week

• Adverse events

  Through study completion, an average of once a week

• Deaths

  Every 3 months for up to 12 months after completing study treatment

• Incidence of clinical laboratory abnormalities per CTCAE

  Through study completion, an average of once a week

Study Arms (3)

Arm A: Recurrent Grade 4 Glioma Surgical Cohort Time Escalation

EXPERIMENTAL

Drug: AZD1390

Arm B: Recurrent Grade 4 Glioma Dose Escalation

EXPERIMENTAL

Drug: AZD1390

Arm C: Newly-diagnosed Grade 4 Glioma

EXPERIMENTAL

Drug: AZD1390

Interventions

AZD1390 DRUG

Phase 0: AZD1390 administered orally daily for 3 days prior to resection Phase 1b: AZD1390 administered daily for 5 days concurrently with standard of care radiation therapy

Arm A: Recurrent Grade 4 Glioma Surgical Cohort Time Escalation; Arm B: Recurrent Grade 4 Glioma Dose Escalation; Arm C: Newly-diagnosed Grade 4 Glioma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• a. Arm C only: Participants undergoing resection for a suspected newly diagnosed WHO Grade 4 glioma. Participants will also need to have radiation planned as part of the post-surgical treatment plan; OR,
• b. Arms A and B only: Participants who have had a prior resection of diagnosed glioma (2021 WHO grade IV), defined as participants who have progressed on or following standard therapy, which includes maximal surgical resection, temozolomide, and fractionated radiotherapy. Participants will also need to have radiation planned as part of the post-surgical treatment plan.
• \. Participants must have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm.
• \. Provision of signed and dated, written informed consent (personally or by the legally authorized representative, if applicable) prior to any study specific procedures, sampling and analyses.
• \. Age ≥18 at time of consent. 5. Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology (Group (ECOG) scale1.
• \. Ability to swallow oral medications. 7. Participant has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):
• Adequate bone marrow function:
• absolute neutrophil count ≥1,500/mcL
• Platelets (at time of surgery) ≥100,000/mcL
• hemoglobin ≥9.0 g/dL Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
• Adequate hepatic function:
• o total bilirubin ≤1.5 X ULN. Participants with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.
• o AST(SGOT) ≤2.5 X institutional ULN
• o ALT(SGPT) ≤2.5 X institutional ULN
• Adequate pancreatic function:

You may not qualify if:

• Current use of coumarin-derived anticoagulant for treatment, prophylaxis or otherwise, that cannot be discontinued prior to surgery. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed.
• Pregnancy or lactation.
• Known allergic reactions to components of the AZD1390.
• Known to have active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis, as determined by the investigator.
• Known active systemic bacterial infection (requiring intravenous \[IV\] antibiotics or fever \>38.5°C at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening of viral infection is not required for enrollment.
• The participant has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• Any of the following cardiac criteria:
• Cardiac dysfunction defined as: Myocardial infarction within six months of study entry, NYHA Class II/III/IV heart failure, unstable angina or unstable cardiac arrhythmias.
• Mean resting corrected QT interval (QTcF) \> 470 msec obtained from 3 electrocardiograms (ECGs) (QTc interval will be calculated using Fridericia's formula).
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, e.g., complete left bundle branch block, third degree heart block.
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age. Patients stable on concomitant medications known to prolong the QT interval may be allowed to participate in the study provided that their mean resting corrected QT interval (QTcF) is \< 470 msec at baseline and after discussion with the Medical Monitor.
• History of epileptic disorder or any seizure history unrelated to tumor.
• History or presence of myopathy or raised creatine kinase (CK) \>5 x upper limit of normal (ULN) on 2 occasions at screening.
• Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
• Participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).

Sponsors & Collaborators

• Nader Sanai: lead
• AstraZeneca: collaborator
• Barrow Neurological Institute: collaborator
• Ivy Brain Tumor Center: collaborator

Study Sites (1)

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

Related Links

• Ivy Brain Tumor Center Website

MeSH Terms

Conditions

Glioblastoma; Glioma

Interventions

AZD1390

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Nader Sanai, MD

  Chief Scientific Officer/Director

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of the Ivy Brain Tumor Center

Study Record Dates

• First Submitted: December 22, 2021
• First Posted: January 10, 2022
• Study Start: May 27, 2022
• Primary Completion (Estimated): June 10, 2026
• Study Completion (Estimated): December 10, 2026
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)