Glioblastoma - Brain Tumor
Conditions
Interventions
On Day 0 of the study, the patient will receive their first dose of 131-IPA by
intravenous infusion. On Day 7 standard treatment will start with chemotherapy
(temozolomide=TMZ) and radiotherapy and
Sponsors
Telix Pharmaceuticals (Innovations) Pty Ltd
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Understand and voluntarily sign the informed consent form prior to any study relatedprocedure and/or assessments being conducted. 2. Are Male or Female, and aged 18 and older, at the time of signing the informed consent. 3. Have histologically confirmed intracranial glioblastoma (per WHO 2021 definition) following surgical resection. Tumours primarily localised in the infratentorial compartment will be excluded. 4. Have had prior surgery for glioblastoma, but no systemic therapy or radiation therapy for GBM. 5. Have a Karnofsky Performance Status >=70. 6. Plan to begin chemoradiation therapy 3-6 weeks after surgical resection with Stupp regimen. 7. Have adequate organ function at Screening: 7.1 Bone marrow: 7.1.1 Leukocytes >=3x10^9/L 7.1.2 Absolute neutrophil count >=1.5x10^9/L 7.1.3 Platelets >=100x10^9/L 7.1.4 Haemoglobin >=9g/dL 7.2 Liver function: 7.2.1 Total bilirubin =50 mL/min 8. Have at least 6 slides without staining or a tissue block (frozen or paraffin-embedded) available from a previous biopsy or surgery (tumour sample previously archived). 9. Have the capacity to understand the study and be able and willing to comply with all protocol requirements, including compliance with the radiation protection guidelines (including hospital admissions and isolation) that are applied by the treating institution to protect their contacts and the public. 10. Agree to practice adequate precautions to prevent pregnancy to avoid potential problems associated with radiation exposure to the unborn child. 11. Females must have a negative pregnancy test at screening and on dosing day, must not be lactating.
Exclusion criteria
Exclusion criteria: 1. Are unable to provide signed informed consent 2. Have had prior treatment for glioma, excluding surgery. 3. Are unable to undergo contrast-enhanced MRI. 4. Intend to be treated with tumor-treating fields prior to progression. 5. Have a history or evidence of delayed-type hypersensitivity (DTH)-dependent chronic infection (e.g., tuberculosis, systemic fungal or parasitic infection), potentially exacerbating under systemic corticoid therapy. 6. Have a known history of allergy TMZ, any excipient in the study medication or any other intravenously administered human proteins/peptides/antibodies. 7. Have haemostaseologic conditions, precluding catheterisation or invasive procedures. 8. Have phenylketonuria 9. Have any medical condition that in the opinion of the Investigator may interfere with the participant*s ability to adhere to the study or may impose a risk to the participant*s health. 10. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery) within 3 weeks of administration of study treatment except surgery on primary tumour. 11. Pregnant, breastfeeding or planning to get pregnant during the duration of the study. 12. Requirement of chronic administration of high dose corticosteroids or other immunosuppressant drugs. Limited or occasional use of corticosteroids to treat or prevent acute adverse reactions is not considered an exclusion criterion. 13. Have presence of active and uncontrolled infections or other severe concurrent disease, which, in the opinion of the investigator, would place the participant at undue risk or unable to comply with study requirements. HIV-positive participants may be included in the study if they are on a stable dose of anti-retroviral therapy. 14. Have concurrent malignancies (except: basal cell carcinoma, in situ breast cancer) unless the patient has been disease-free without intervention for at least 2 years. 15. Have taken growth factors or immunomodulatory agents within 7 days prior to the administration of study treatment. 16. Have serious, non-healing wound, ulcer, or bone fracture. 17. Have a requirement of concurrent use of other anti-cancer treatments or agents other than study medication. 18. Have received any other IMP within 90 days prior to the planned administration of study drug. 19. Have uncontrolled Hashimoto*s or Grave*s disease 20. Have on-going and unresolved Grade >= 1 AEs following surgical resection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - To determine the safety and tolerability of 131I-TLX-101 in combination with standard of care treatment in newly diagnosed Glioblastoma (GBM) patients, by determining the Dose Limiting Toxicities (DLT), Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D). This will be done by assessing TEAEs type (treatment emergent adverse events) type according to MedDRA, frequency, severity according to NCI CTCAE V5.0, seriousness, and relationship of study treatment will be assessed. Laboratory abnormalities will be assessed according to the NCI CTCAE V5.0. - Incidence rate and the grade (severity) of DLTs based on the occurrence of Adverse Events (AEs) reported according to the NCI CTCAE v5.0. DLTs include any grade >= 3 events considered possibly related to the study drug, but excludes cerebral oedema, and haematological toxicity. | — |
Secondary
| Measure | Time frame |
|---|---|
| - 1-year overall survival rate of patients treated with 131I-TLX-101 plus standard of care treatment. - 2-year overall survival rate of patients treated with 131I-TLX-101 plus standard of care treatment. - To determine Progression Free Survival (PFS) from the date of enrolment to the date of progression or death for any cause, whichever comes first, assessed up to 51±1 weeks. - To determine best Objective Response Rate (ORR) in patients with partial response at weeks 7, 15, 23, 31, 43±1, and 51±1 as defined by modified Response in Neuro-Oncology (mRANO)* criteria. - To determine ORR in patients with stable disease at weeks 7, 15, 23, 31, 43±1, and 51±1 as defined by mRANO criteria - To determine safety throughout study completion for each participant, for a minimum of 51±1 weeks - To determine Quality of Life (QoL) as determined using the EORTC QLQ-C30 questionnaire and Quality of Life Questionnaire - Brain Neoplasm (QLQBN20) questionnaires, and neurocognitive tests: Controlled Oral Word Association Test (COWA test), Hopkins Verbal Learning Test-Revised (HVLT-R test), and Trail Making Test (TMT) | — |
Countries
Netherlands
Outcome results
None listed