NCT03423628

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

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 180 (estimated)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 130 Years
• Healthy volunteers: Not accepted

Summary

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

Detailed description

This first time-in patients (FTIP), open-label, multicentre study of AZD1390 will be conducted in the United States, the United Kingdom and Japan. It consists of three treatment arms: Arm A, B, C. The Japan dose confirmation part (Japan part) is a sub-study of Arm A. Sites from Japan will only participate in the Japan part. This Phase 1 study will assess safety and tolerability of AZD1390 in combination with radiation therapy (RT) in brain malignancies. The combination cohorts have been designed to assess escalating cumulative doses of AZD1390 in settings with 3 different radiation treatment regimens: * 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

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

Interventions

Type	Name	Description
RADIATION	Radiation Therapy	35 Gy of Intensity-modulated radiation therapy (IMRT) administered at daily fractions of 3.5 Gy over 10 fractions (2 weeks)
DRUG	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	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	Radiation Therapy	60 Gy of intensity- modulated radiation therapy (IMRT) administered at daily fractions of 2 Gy over 30 fractions (6 weeks)
DRUG	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.
DRUG	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.

Timeline

• Start date: 2018-04-02
• Primary completion: 2026-09-16
• Completion: 2026-09-16
• First posted: 2018-02-06
• Last updated: 2025-12-22

Locations

12 sites across 3 countries: United States, Japan, United Kingdom

Regulatory

• FDA-regulated drug study