Testing 123I-ATT001, a new type of targeted radiotherapy, administered directly to the brain tumour of patients in whom the glioblastoma has returned after previous treatment
- Conditions
- Relapsed glioblastomaCancer
- Registration Number
- ISRCTN78231121
- Lead Sponsor
- Theragnostics Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 69
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Part 1 only:<br>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).<br>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 Outcome Measures
Name Time Method