Newly-diagnosed primary glioblastoma Cancer
Conditions
Interventions
COMBAT- GB is a phase 1, non-randomised, dose escalation trial. It is looking for an effect of the “enhancer” drug ASTX727, given before immunotherapy (nivolumab), on patient outcomes and tumour respo
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Age
18 Years to 120 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 05/03/2026: 1. Aged 18 years and over on day of signed informed consent 2. Ability to provide written informed consent. 3. Willing and able to comply with the protocol scheduled follow-up visits and examinations for the duration of the trial. 4. WHO Performance status 0-1 5. Newly suspected glioblastoma on Gadolinium-enhanced MRI scan and reviewed in the local Neuro-oncology multidisciplinary meeting, which is amenable for maximal resection. 6. Patients with tumours that do not exert significant mass effect and/or have significant oedema and where a delay to surgery is thought will lead to undue harm as determined by the MDT. 7. Male and female participants of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception requirements whilst receiving decitabine/nivolumab and for 6 months after their last dose of decitabine for female participants and for 3 months after their last dose of decitabine for male participants. ----- Previous inclusion criteria as of 07/03/2024: 1. Aged 18 years and over on day of signed informed consent 2. Ability to provide written informed consent. 3. Willing and able to comply with the protocol scheduled follow-up visits and examinations for the duration of the trial. 4. WHO Performance status 0-1 5. Newly suspected glioblastoma on Gadolinium-enhanced MRI scan and reviewed in the local Neuro-oncology multidisciplinary meeting, which is amenable for maximal resection. 6. Patients with tumours that do not exert significant mass effect and/or have significant oedema and where a delay to surgery is thought will lead to undue harm as determined by the MDT. 7. Male and female participants of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception requirements whilst receiving ASTX727/Nivolumab and for 6 months after their last dose of ASTX727 for female participants and for 3 months after their last dose of ASTX727 for male participants. ----- Previous inclusion criteria: 1. Aged 16 years and over on day of signed informed consent 2. Ability to provide written informed consent. 3. Willing and able to comply with the protocol scheduled follow-up visits and examinations for the duration of the trial. 4. WHO Performance status 0-1 5. Newly suspected glioblastoma on Gadolinium-enhanced MRI scan and reviewed in the local Neuro-oncology multidisciplinary meeting, which is amenable for maximal resection. 6. Patients with tumours that do not exert significant mass effect and/or have significant oedema and where a delay to surgery is thought will lead to undue harm as determined by the MDT. 7. Male and female participants of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception requirements whilst receiving ASTX727/Nivolumab and for 6 months after their last dose of ASTX727 for female participants and for 3 months after their last dose of ASTX727 for male participants.
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 05/03/2026: 1. Patients with suspected glioblastoma who have significant mass effect and need emergency surgery. 2. Any concern on initial MRI that the tumour may not be a primary glioblastoma. 3. Patients that have previously received immunotherapy or hypomethylating agents. 4. Impaired gastrointestinal function that may significantly alter absorption of decitabine. 5. Has a known diagnosis of immunodeficiency (human immunodeficiency virus [HIV] 1/2 antibodies) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment excluding steroids. 6. Another advanced malignancy or history of another early malignancy that the investigator considers is likely to impact life expectancy. 7. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease. Patients with vitiligo, resolved childhood asthma/atopy/psoriasis or hypothyroidism stable on hormone replacement would be an exception. Patients that require intermittent use of bronchodilators or local steroid injections are not excluded. 8. Has evidence of or a history of interstitial lung disease or (non-infectious) pneumonitis. 9. History of severe allergic reactions to any unknown allergens or any components of the trial drugs. 10. Is pregnant or breastfeeding or expecting to conceive children within the projected duration of the trial, starting with the screening visit through 6 months after the last dose of trial treatment for female participants, or is expecting to father children in that time through 3 months after the last dose of trial treatment for male participants. 11. Has known active hepatitis B or hepatitis C. 12. Concurrent or recent (<28 days) treatment in any other interventional clinical trial involving novel surgical technique or medication. 13. Any psychological, social or medical condition, physical examination finding or laboratory abnormality that in the judgement of the Investigator is likely to interfere with participation in the trial. 14. Any condition that, in the clinical judgment of the treating physician, is likely to interfere with evaluation of trial treatment, interpretation of subject safety or trial results, prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk. Previous exclusion criteria: 1. Patients with suspected glioblastoma who have significant mass effect and need emergency surgery. 2. Any concern on initial MRI that the tumour may not be a primary glioblastoma. 3. Patients that have previously received immunotherapy or hypomethylating agents. 4. Impaired gastrointestinal function that may significantly alter absorption of ASTX727. 5. Has a known diagnosis of immunodeficiency (human immunodeficiency virus [HIV] 1/2 antibodies) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment excluding steroids. 6. Another advanced malignancy or history of another early malignancy that the investigator considers is likely to impact life expectancy. 7. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease. Patients with vitiligo, resolved childhood asthma/atopy/psoriasis or hypothyroidism stable on hormone replacement would be an exception. Patients that require intermittent use of bronchodilat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Safety profile of ASTX727/Nivolumab combination therapy measured at baseline, after neoadjuvant cycle of ASTX727/nivolumab (up to 4 weeks after first dose of ASTX727), then monthly up to 4 months following ASTX727/nivolumab 2. To determine the maximum tolerated dose (MTD) of ASTX727 when combined with nivolumab for the neoadjuvant treatment of participants with primary glioblastoma (the dose associated with no more than 25% DLT rate) measured from first dose of ASTX727 to 28 days following first dose ASTX727 or surgery, whichever is shortest | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Clinical efficacy of combination ASTX727/nivolumab. Measured using progression free survival after surgery, 1 year survival rate, Overall Survival Time from diagnosis to death. Patients with no death recorded will be censored at last known alive time 2. Rate of delayed surgery due to drug toxicity for patients receiving combination ASTX727/Nivolumab therapy measured form time to surgery from first dose of ASTX727 Tertiary: 1. Paired whole exome sequencing, RNAseq and Methylation array. 2. Immunohistochemistry, focusing on the amount of T cell infiltration and location of T cells. Single cell phenotyping and TCR sequencing of tumour infiltrating lymphocytes. Testing for tumour specific T cells. 3. Phenotyping of peripheral blood mononuclear cells | — |
Countries
England, United Kingdom, Wales
Contacts
Public ContactStudy Team
Outcome results
None listed