Relapsed glioblastoma Cancer
Conditions
Interventions
Part 1 - Monotherapy of 123I-ATT001
Dose 1: 500 MBq of 123I-ATT001 administered intercranially via an Ommaya Reservoir once a week for four weeks.
Dose 2: 800 MBq of 123I-ATT001 administered intercr
Sponsors
Theragnostics Limited
Eligibility
Sex/Gender
All
Age
18 Years to 66 Years
Inclusion criteria
Inclusion criteria: 1. Ability to give written informed consent as evidenced by signature on the subject consent form, to communicate well with the Investigator, and to comply with the expectations of the study 2. Men and women over 18 years of age 3. Histologically confirmed recurrent glioblastoma (grade IV) as per WHO criteria 2021 (IDH- wild type only) where the subjects have an Ommaya reservoir in an intralesional cavity of at least 5 mL volume 4. Documented recurrent disease (radiological, based on RANO v.1.0) within 3 months before first study drug administration 5. Eastern Cooperative Oncology Group Performance status of 0 or 1 6. Adequate organ function: 6.1. Serum creatinine <1.5x upper limit of normal (ULN) 6.2. Liver function tests: serum bilirubin <1.5xULN (except subjects with known Gilbert’s syndrome: serum total bilirubin must be <3×ULN in these subjects); transaminases <3xULN and <5 in case of liver metastases 6.3. Absolute neutrophil count (ANC) =1000/mL; Platelets =100,000/mL; haemoglobin =9 g/dL or =5.6mmol/L 6.4. International normalisation ratio or prothrombin time =1.5x ULN, unless the subject is receiving anticoagulant therapy 7. Women of childbearing potential must use two forms of reliable contraception before starting 123I-ATT001 treatment, during therapy and for 6 months after receiving the last dose of 123I-ATT001. Two highly effective and complementary forms such as hormonal birth control, and intrauterine devices with supplementary barrier methods are recommended. Male subjects and their female partners of childbearing potential should use reliable contraception such as hormonal birth control, and intrauterine devices with supplementary barrier method (male condom) during therapy and for 6 months after receiving the last dose of 123I-ATT001. All male subjects must agree to not donate sperm during the study and for 6 months after the last dose of the study drug. 8. Be able to understand and comply with the requirements of the study, as judged by the Investigator
Exclusion criteria
Exclusion criteria: 1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment 2. Diagnosis of immunodeficiency or receiving systemic steroid therapy of up to 4 mg/ day dexamethasone or equivalent or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment 3. Prior anticancer treatments within the following periods: 3.1. Chemotherapy within 4 weeks of enrolment or 5 half-lives, whichever is shorter 3.2. Targeted small molecule therapy within 4 weeks of enrolment or 5 half-lives, whichever is shorter 3.3. Immunotherapy (including monoclonal antibody therapy) or radiation therapy within 4 weeks before study day 1 4. Unresolved NCI-CTCAE grade 2 or higher toxicity (except stable neurological toxicities/deficits related to disease process, alopecia) 5. Patients with a known allergy to Olaparib or Iodine 6. Known additional malignancy that is progressing or requires active treatment except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer 7. Any condition that precludes the proper performance of SPECT and/or MRI scan: 7.1. Subjects who are not able to tolerate the contrast agent 7.2. Subjects with metal implants or arthroplasty, or any other objects that might interfere with the MRI analysis 7.3. Subjects unable to raise arms for prolonged imaging purposes 7.4. Subjects unable to lie still for the entire imaging time 7.5. Subjects weighing greater than 130 kg (287 lb) 8. Any clinically significant abnormalities in resting ECG at the time of screening including prolonged QTcF (>450 ms for males; >470 ms for females) and cardiac arrhythmias, as judged by the Investigator or designee 9. Unstable systemic disease (including but not limited to active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease) 10. Psychiatric, substance misuse or functional disorders that prevent subjects from providing informed consent, following protocol instructions or cooperating with the requirements of the study 11. Active infection requiring systemic therapy 12. Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 3 months after the last dose of study treatment 13. Subject that has a condition or is in a situation, which in the investigator's opinion may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject’s participation in the study 14. History of non-infectious pneumonitis within the last 3 years
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1 only: 1. Safety and tolerability will be evaluated by monitoring of adverse events, vital signs, performance status, clinical laboratory assessments, electrocardiograms, review of concurrent illness, concomitant medication, weight and physical examination findings. This will be performed from screening to the end of the treatment visit (28 days after the last dose of 123I-ATT001). 2. To determine the recommended dose of 123I-ATT001 via intracavitary direct instillation in subjects with relapsed glioblastoma, both as monotherapy and in combination with other anticancer therapies. The incidence of dose-limiting toxicity (DLT) will be evaluated by monitoring adverse events from day 1 to day 15 of 123I-ATT001 administration (pre-third dose). | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1 only: 1. To determine the biodistribution and pharmacokinetics of 123I-ATT001, blood and urine samples will be collected from the first 6 patients in Part 1. Blood will be collected 1 hour, 4 hours and 24 hours post each dose and optionally at 48 hours post first dose. Urine will be collected only 24 hours post first dose. 2. To determine the radiation dosimetry of 123I-ATT001 (exposure of each organ to radiation): 2.1. Whole body and brain SPECT/CT imaging will be performed 1-hour post each dose 2.2. Whole body and brain SPECT at 4 hours post each dose 2.3. Brain only SPECT will be done 24 hours post-injection of the first dose 2.4. An optional brain SPECT image may be taken 48 hours post-injection of the first dose 2.5. Brain only SPECT will be done at 4 hours ±30min post-injection of the fourth dose 3. To obtain a preliminary assessment of the antitumour activity of 123I-ATT001 RANO response criteria using MRI Scans will be assessed at screening, day 14 post each dose, end of treatment visit, then a further 3 times every 8 weeks at follow up. 4. To evaluate the effect of 123I-ATT001 on neurological function according to NANO criteria at screening and then pre-dose on the day of the 1st, 3rd and 5th (if given) and at the end of the treatment visit. Additionally, patients will complete the MDASI-BT questionnaire at screening (after surgery) and then pre-dose on the day of the 1st, 3rd and 5th (if given) and at the end of the treatment visit. | — |
Countries
United Kingdom
Contacts
Public ContactTrial team -
Outcome results
None listed