Glioblastoma Cancer
Conditions
Interventions
The clinical trial will be divided into two parts: Phase 1b (proof of concept of hypothesis-driven biomarker-guided therapies) and Phase 2 (preliminary efficacy testing).
This is a study within 5G: A
Sponsors
Institute of Cancer Research
Eligibility
Sex/Gender
All
Age
16 Years to 99 Years
Inclusion criteria
Inclusion criteria: Phase 1b: 1. Patients with: 1.1. Glioblastoma, IDH-wildtype Grade 4 2. Patients for Phase 1b will need to have consented to the Minderoo Precision Brain Tumour Programme and have available whole genome and transcriptome data available. 3. Patients for the front-line minimal residual disease (MRD) cohort will be eligible following completion of optimal surgery and Stupp-based adjuvant chemoradiotherapy as long as they meet all other inclusion/exclusion criteria. 4. Aged 16 years or over. 5. Life expectancy of at least 12 weeks. 6. World Health Organisation (WHO) performance status of 0–1. 7. Neurologically stable (eg without a progression of neurological symptoms or requiring escalating doses of systemic steroid therapy within the last week prior to informed consent). 8. Written (signed or dated) informed consent and be capable of co-operating with treatment and follow-up. 9. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week prior to the first dose of either IMP. 9.1. Haemoglobin (Hb): = 9.0 g/dL 9.2. Absolute neutrophil count: =1.5 x 10^9/L 9.3. Platelet count: =100 x 10^9/L 9.4. Coagulation: INR 7 days within intended therapeutic range if anticoagulated 9.6. Bilirubin: Within institution normal ranges 9.7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): <3 x ULN 9.8. Albumin: =28 g/dL 9.9. Creatinine: <1.5 x ULN 9.10. Sodium: =130 mmol/L 9.11. Potassium, Calcium, Magnesium, phosphate: Within institution normal ranges (replacement is permitted) 9.12. HbA1C (%): <8.0 9.13. Urinary protein: <1+ on dipstick 10. Female patients with reproductive potential must have a negative serum pregnancy test within 14 days prior to the start of the trial. 11. Men and women of childbearing potential must agree to comply with the use of a highly effective method of contraception so as to avoid impregnating a partner or becoming pregnant, respectively, during the study and for at least 150 days after the last dose of either investigational drug. Phase 2: Patients with any other CNS tumours will only be eligible for defined Phase 2 biomarker arms once a Phase 1b GO decision has been met. Specific eligibility criteria for these tumours will be defined following an amendment.
Exclusion criteria
Exclusion criteria: Phase 1b: 1. Receipt of treatment before the first dose of the study drug (Cycle 1 Day 1) within an interval shorter than the following, as applicable: 1.1. Cytotoxic chemotherapy during the prior 2 weeks or 6 weeks for nitrosoureas 1.2. Bevacizumab during the prior 6 weeks 1.3. Five half-lives of any small molecule investigational or licensed medicinal product. 2. Prior immune checkpoint inhibitor therapy or vaccine therapy is not permitted. Prior use of any other immune-modulatory investigational agent must be discussed with sponsor team and CI. 3. Ongoing Grade 2 or greater toxicities from pre-existing conditions or from previous treatments. 4. Patients with carcinomatous meningitis, leptomeningeal spread of tumour, spread of tumour to the brain stem or spinal cord. 5. Has evidence of recent intratumoural or peritumoural haemorrhage on baseline MRI. Patients with radiological findings that are stable on at least 2 consecutive MRI scans at least 3 weeks apart will be eligible. 6. History of clinical relevant bleeding disorders, including significant GI bleeding within the last 6 months. 7. History of arterial thromboembolism. 8. Recent (within 3 months) deep vein thrombosis or pulmonary embolism or other significant thromboembolism. Venous port of catheter thrombosis or superficial thrombosis are not considered significant. Patients with prior thrombosis (> 3 months ago) on stable anticoagulation are permitted to be enrolled. 9. History of clinically significant cardiac disorders: 9.1. Myocardial infarction, or New York Heart Association Class II to IV congestive heart failure, within 6 months of the first dose of the study drug. 9.2. Concurrent and clinically significant abnormalities on ECG at Screening, including a corrected QT interval (QTcF >480ms). 10. History of malabsorption syndrome or other conditions that may interfere with enteral absorption. Patients with a history of or active inflammatory bowel disease (eg Crohn’s disease or ulcerative colitis). History of gastrointestinal perforation or fistulae. 11. History of uncontrolled diabetes. Patients with controlled diabetes on therapy with HbA1C 1g/24 hours. Participants with >1+ on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. 13. Has significant lung disease including pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, active tuberculosis, or history of opportunistic infections (including PCP or CMV pneumonia). 14. Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV). 15. Steroid requirement for neurological symptom control of >3mg Dexamethasone per day (patients will be allowed to enrol if they have been on a stable dose of steroids of equivalent or less than 3mg Dexamethasone for at least 5 days prior to Day 1 of Cycle 1). 16. Has received a live vaccine within 30 days of the planned start of study therapy. Note: inactive vaccines including COVID vaccines are allowed prior to 1 week of Day 1 of Cycle 1). 17. Current active concurrent malignancy. Cancer survivors who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease recurrence for three years or more and are deemed at negligible risk of recurrence will be eligible. 18. Is a participant or plans to participate on another interventional clinical trial while taking part in thi
Countries
England, Scotland, United Kingdom
Contacts
Public Contact- 5G Team
Outcome results
None listed