Phase I open-label trial of 123I-ATT001 monotherapy and in combination with treatment therapies in subjects with relapsed glioblastoma.
The main goals of this study are to understand if 123I-ATT001 is safe and tolerable to treat participants with relapsed glioblastoma and to determine the maximum tolerated dose that can be given to participants without any unacceptable side effects. The study consists of two parts: \- Part 1 is a dose escalation study where three doses of 123I-ATT001 will be tested, starting with the lowest dose. When a recommended dose (RD) has been declared, a monotherapy expansion cohort will be open at that dose level. In Part 1 participants will receive a 123I-ATT001 dose, once per week, for four weeks (+ two optional extra cycles). * Part 2 is a dose expansion study where one dose of 123I-AT001 will be tested in combination with other therapies. Part 2 will begin after the Part 1 has completed and a recommended part 2 dose has been chosen. The specific details and combination therapies for Part 2 of the study will be added via a protocol amendment at a later date.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
123I-ATT001
University College London Hosptial
London, United Kingdom
University Hospital Southampton
Southampton, United Kingdom
Part 1 - Dose Escalation: Frequency and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
To assess safety and tolerability of 123I-ATT001
Time frame: Screening to end of treatment visit (28 days after last dose of 123I-ATT001)
Part 1- Dose Escalation: Incidence of Dose Limiting Toxicity (DLT)
Evaluated by monitoring of Adverse Events.
Time frame: Day 1 to Day 14 of 123I-ATT001 administration
Part 1 - Dose Escalation: biodistribution and pharmacokinetics of 123I-ATT001 in blood
Blood samples will be collected from the first 6 patients in Part 1.
Time frame: Collected 1 hour, 4 hours and 24 hours post each dose and optionally at 48 hours post first dose.
Part 1- Dose Escalation: biodistribution and pharmacokinetics of 123I-ATT001 in urine.
Urine samples will be collected from the first 6 patients in Part 1.
Time frame: Collected 24 hours post first dose
Part 1 - Dose Escalation: radiation dosimetry of 123I-ATT001 (exposure of each organ to radiation)
SPECT/CT and or whole body planar imaging
Time frame: 1 and 4 and 24 hours post first dose and 4 hours post fourth dose.
Part 1- Dose Escalation: preliminary assessment of the antitumour activity of 123I-ATT001
Efficacy will be assessed according to the RANO response criteria using MRI Scans
Time frame: Screening, Day 14 post each dose, 28 days after last dose, then a further 3 times every 8 weeks at follow up.
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Part 1 - Dose Escalation: effect of 123I-ATT001 on neurological function
Neurological function will be assessed by the principal investigator according to NANO criteria.
Time frame: Screening, the day of the 1st, 3rd and 5th (if given) dose, may also be performed within 48 hours prior to dose administration. It will also be performed on the End of Treatment visit which takes place 28 days post last dose.
Part 1 - Dose Escalation: effect of 123I-ATT001 on neurological function
Patients will complete the MDASI-BT questionnaire
Time frame: Screening, the day of the 1st, 3rd and 5th (if given) dose, may also be performed within 48 hours prior to dose administration. It will also be performed on the End of Treatment visit which takes place 28 days post last dose.