AZD1390 in combination with radiation therapy

• Research type

  Research Study

• Full 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

• IRAS ID

  241460

• Contact name

  Anand Achanta

• Sponsor organisation

  AstraZeneca

• Eudract number

  2017-002451-28

• Clinicaltrials.gov Identifier

  NCT03423628

• Duration of Study in the UK

  2 years, 10 months, 3 days

• Research summary

  This study will test AZD1390 in combination with radiation therapy (RT) for the treatment of brain malignancies. AZD1390 stops the repair of damaged DNA in cancer cells by blocking activation of ATM, a protein involved in DNA repair following RT. AZD1390 is predicted to penetrate the brain. Studies in animal models of brain tumours have shown that when given during and after irradiation, AZD1390 makes RT more effective. In this first time in patient (FTIP) study, AZD1390 will be given to brain tumour patients to test the safety, tolerability and pharmacokinetics (PK, the study of the way the body absorbs, distributes and eliminates a drug) of increasing doses of AZD1390 with different regimens of RT. Each of the three arms in this study provides standard of care RT for the disease setting indicated below:
  • Arm A: patients with recurrent glioblastoma multiforme (GBM) that are eligible for re-irradiation at a cumulative dose of 35 Gy with intensity-modulated RT (IMRT) over 2 weeks.
  • Arm B: patients with tumours that have spread to the brain scheduled to receive 30 Gy of whole brain RT over 2 weeks
  • Arm C: a specific subset of patients with newly diagnosed GBM who receive 60 Gy of IMRT over 6 weeks.

  Patients in each arm will also receive a single dose of AZD1390 followed by PK analysis before RT, and two weeks of AZD1390 following completion of their RT course. During the study, opening of sequential arms will have specific safety triggers that are detailed in the clinical study protocol, and dose escalations will be based upon the safety profile and available PK data from all cohorts open in the study. The eligibility criteria, proposed doses, and safety monitoring detailed in the clinical study protocol have been carefully selected to appropriately mitigate the risk to patients.

• REC name

  London - City & East Research Ethics Committee

• REC reference

  18/LO/0544

• Date of REC Opinion

  11 May 2018

• REC opinion

  Further Information Favourable Opinion