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
AstraZeneca
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
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 r…
Eligibility
- Age range
- 18–130 years
- Sex
- All
- Healthy 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 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. *…
Interventions
- RadiationRadiation Therapy
35 Gy of Intensity-modulated radiation therapy (IMRT) administered at daily fractions of 3.5 Gy over 10 fractions (2 weeks)
- DrugAZD1390
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.
- RadiationRadiation 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).
- RadiationRadiation Therapy
60 Gy of intensity- modulated radiation therapy (IMRT) administered at daily fractions of 2 Gy over 30 fractions (6 weeks)
- DrugAZD1390
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.
Locations (12)
- Research SiteBoston, Massachusetts
- Research SiteBoston, Massachusetts
- Research SiteNew York, New York
- Research SitePittsburgh, Pennsylvania
- Research SiteRichmond, Virginia
- Research SiteChūōku