Combination nivolumab and decitabine for treatment of primary glioblastoma
Trial ID: ISRCTN30298528
Other - Phase 1 - Recruiting
Background and study aims
Glioblastoma is the most common brain cancer in adults and unfortunately is life-limiting. It is most common in older patients with an average age of 55 at diagnosis. However, it can still affect young adults and even children. Currently, there is no cure for this type of brain tumour. The current gold standard treatment consists of having surgery to remove all of the visible tumour followed by chemotherapy and radiotherapy. Survival rates are better for younger patients (aged under 40) but remain generally poor, with 50% of patients only surviving 2 years from diagnosis.
There is a new set of drugs, termed immunotherapies, that aim to boost the body’s own immune system to fight cancer. Immunotherapies have been shown to increase survival from certain cancers such as skin cancer and lung cancer. However, these drugs, on their own, do not have much effect on glioblastoma. Our research in Oxford has shown that the addition of an additional drug (enhancer drug) to the immunotherapy drug can potentially boost the effect of immunotherapy.
Who can participate?
Patients aged 18 years or older with newly suspected glioblastoma
What does the study involve?
We want to run a phase I safety study to look at the safety of giving a combination of nivolumab (immunotherapy drug) and decitabine (enhancer drug). Phase I studies aim to find the best dose of a new drug with the fewest side effects. Doctors start by giving very low doses of the drug to a few patients. This dose is gradually increased a little bit at a time in different groups of patients to help find the best dose with the least side effects. This will be a small trial to establish whether this combination is safe and to look for the best possible dose. Nivolumab has been given to patients in the past with glioblastoma and decitabine has been given to patients with leukaemia. This combination has not been tried together before in patients with glioblastoma, so it is important that we conduct this small trial first.
What are the possible benefits and risks of participating?
Risks from IMP:
The combination of decitabine and nivolumab has not been given together for patients with glioblastoma, so there's a small chance of an unknown side effect or an increase in any of the known side effects.
However, both drugs have been given separately and have been shown to have different side effect profiles (mainly blood disorders for the enhancer drug decitabine and gut and skin problems for nivolumab), so we do not anticipate a large overlap of side effects. As we are giving this combination before surgery, there is a small chance that surgery may have to be delayed for the side effects to settle, this is likely to be 1-2 weeks if surgery must be delayed.
To try and prevent this, patients will be screened, and the trial only offered to those that are not deemed to be at higher risk of side effects as determined by the inclusion/exclusion criteria. The decitabine will be starting initially at a very low dose in the first participant and will increase the dose per participant slowly as more safety data is gathered during the trial. Participants will come into hospital weekly for a clinical review.
Extra visits and tests:
Participants will attend the hospital more frequently than the standard of care. They will have extra visits for baseline, for the administration of the decitabine, for the check-up and administration of nivolumab and for 2 further visits to monitor their response to the trial drugs. At each of these visits, participants will have additional checks and blood samples taken for safety monitoring and translational research. They will also have monthly follow up reviews until 4 months after their standard of care surgery to resect their tumour, these will also involve additional checks and blood tests taken for safety monitoring and translational research.
For the participants who choose to have the optional research biopsy, they will also have a pre-biopsy MRI for surgical planning purposes and may be admitted the night before their biopsy and remain an inpatient for a night post-biopsy, depending on local protocols. They will also have a CT scan prior to discharge to assess any complications from the biopsy surgery.
Extra samples:
Alongside the optional research biopsy of the tumour, participants will have blood taken at most visits for translational research purposes. Where possible these will be taken alongside standard of care blood tests to minimise discomfort and inconvenience to participants.
Where is the study run from?
University of Oxford (UK)
When is the study starting and how long is it expected to run for?
April 2026 to March 2029
Who is funding the study?
Cancer Research UK
Who is the main contact?
combatgb@nds.ox.ac.uk
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-nivolumab-decitabine-brain-tumour-glioblastoma-combat-gb
Conditions
- Newly-diagnosed primary glioblastoma
- Cancer
Interventions
- ASTX727 (standard dose (SD) tablet) [cedazuridine, Decitabine], nivolumab, ASTX727 (low dose (LD) tablet) [cedazuridine, Decitabine], Decitabine
Eligibility
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.
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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.
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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
- 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 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.
Sponsor
University of Oxford
Source: https://www.isrctn.com/
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