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

Trial ID: ISRCTN78231121

Other - Phase 1 - No longer available

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-a-targeted-treatment-for-glioblastoma-citadel-123 Background and study aims In this study, a type of therapy called targeted radionuclide therapy (TRT) will be used to treat patients with relapsed glioblastoma. The TRT in this study, 123I-ATT001, contains two parts. A radioactive part is a radioactive iodine isotope and a chemical part, which can bind to specific targets (proteins) inside cancer cells to kill them while having a much weaker effect on healthy cells. 123I-ATT001 is a new experimental treatment, meaning it has not been approved by any regulatory authorities, such as the UK’s MHRA. This new treatment will only be available for those enrolled in this study. Who can participate? Patients aged 18 years old and over with relapsed glioblastoma multiforme What does the study involve? 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 the Data Monitoring Committee declare a recommended dose, an additional 8 patients will be recruited at that dose level in Part 1 of the study. In Part 2, one dose of 123I-ATT001 will be tested in a larger group of patients in combination with other therapies. Part 2 will begin after Part 1 has been completed. 123I-ATT001 will be given via an Ommaya reservoir. An Ommaya reservoir is a soft, plastic, dome-shaped device that is placed under the scalp. In Part 1 participants will receive a 123I-ATT001 dose, once per week, for four weeks. Each week is considered a treatment cycle. Any participant who tolerates the 123I-ATT-001 treatments well and shows clinical benefit (e.g., tumour size reduction) may receive up to two additional treatments (one per week). This will be a joint decision between the doctor and the participant. The doctor may decide to reduce the dose or extend the time between treatment cycles in response to any side effects. However, no further treatments will be given in case any unacceptable side effects are observed. The specific details and combination therapies for Part 2 of the study will be added via a substantial amendment at a later date. What are the possible benefits and risks of participating? The study uses an unlicensed drug that also contains radiation. Only trained members of the research team will administer the drug. A radiation expert has reviewed the maximum dose of radiation that a patient could be exposed to and deemed this acceptable. The study also uses ionising radiation in the form of SPECT-CT scans. A radiation expert has reviewed the proposed number of scans and found them to be acceptable. Blood samples also carry risks in terms of possible bruising. Only those who have been appropriately trained in phlebotomy will take samples. There are several visits for this study which may present a time burden to the patients. The sponsor has tried to minimise the number of visits to ensure the minimum burden to the patients. The surgery and installation of the Ommaya reservoir carries the risk of infection and will also mean participants have small bumps on their heads. This procedure is usually carried out as part of the standard of care in this patient population. No additional precautions are needed to be taken by patients after the radiation exposure except pregnancy prevention. Female patients who are pregnant or plan to become pregnant within 3 months following the end of the study, or are breast-feeding, are excluded from the study. Male patients should also not father a baby whilst taking part in the study and for 3 months after the last dose of the study drug. Patients of childbearing potential will have a pregnancy test at the beginning of the study and will be asked to use two highly effective and complementary forms of contraception. Where is the study run from? Theragnostics Limited When is the study starting and how long is it expected to run for? December 2023 to February 2026 Who is funding the study? Theragnostics Limited Who is the main contact? citadel-123@ariceum-therapeutics.com

Conditions

• Relapsed glioblastoma
• Cancer

Interventions

• 123I-ATT001 [123I-ATT001]

Eligibility

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

• 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

Sponsor

Theragnostics Limited

Source: https://www.isrctn.com/

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