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.

JRCT ID: jRCT2051240119

Registered date:02/09/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Recurrent Glioblastoma Multiforme
• Date of first enrollment: 13/09/2024
• Target sample size: 18
• Countries of recruitment: United States,Japan,United Kingdom,Japan
• Study type: Interventional

Intervention(s)

AZD1390 + Radiation Therapy

Drug: AZD1390
- AZD1390 Administered in 3 Cycles:
_ Cycle 0: 1 dose prior to Radiation Therapy.
_ Cycle 1: continuous dosing during Radiation Therapy.
_ Cycle 2: 2 weeks adjuvant treatment after Radiation Therapy.

Radiation: Radiation Therapy
- Japan part: 35 Gy of Intensity-modulated radiation therapy (IMRT) administered at daily fractions of 3.5 Gy over 10 fractions (2 weeks)

Outcome(s)

Primary Outcome

- Incidence of dose-limiting toxicities (DLTs)
DLTs will be used to calculate the maximum tolerated dose (MTD). The MTD of AZD1390 is the maximum dose at which <=25% patients experience a DLT.

- Incidence of adverse events (AEs) and serious adverse events (SAEs)
For each adverse event CTCAE grade and causality (related to AZD1390 or radiotherapy) will be collected.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 130age old
• Gender: Both

Include criteria

- Provision of formalin-fixed paraffin embedded tissue sample from primary or metastatic disease

- Karnofsky Performance Score of 60 or more.

- 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.

Exclude 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 the Japan part.
- 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

Related Information

• Primary Sponsor: Hibi Kazushige
• Secondary ID(s): NCT03423628