Ipilimumab with Temozolomide versus Temozolomide alone after surgery and chemoradiotherapy in patients with recently diagnosed glioblastoma
A Phase II, Open Label, Randomised Study of Ipilimumab with Temozolomide versus Temozolomide alone after surgery and chemoradiotherapy in patients with recently diagnosed glioblastoma
EudraCT Number: 2018-000095-15
ISRCTN Number: ISRCTN84434175
Sponsor: University of Oxford
Chief Investigator: Dr Paul Mulholland, University College London Hospitals
Participating Hospitals: Click Here
This is an unblinded, open labelled stratified randomised Phase II multicentre clinical trial (CTIMP). Patients with newly diagnosed de-novo glioblastoma following surgery or biopsy and radical radiotherapy with concomitant temozolomide will be recruited from 7 sites in the UK. Patients who meet the eligibility criteria will be randomly allocated to receive either ipilimumab and temozolomide (Arm A) or temozolomide alone (Arm B).
Closed to recruitment 12th May 2021
Target: 120 Patients
Arm A: 80 patients
Arm B: 40 patients
Mount Vernon Cancer Centre, Middlesex (Dr Paul Mulholland)
Addenbrooke's Hospital, Cambridge (Dr Fiona Harris)
Western General Hospital, Edinburgh (Dr Sharon Peoples)
Guy’s Hospital, London (Dr Lucy Brazil)
University College Hospital, London (Dr Paul Mulholland)
Churchill Hospital, Oxford (Mr Puneet Plaha)
The Christie, Manchester (Dr Catherine McBain)
- To evaluate whether the addition of ipilimumab to the current standard of care following surgery and chemoradiotherapy will improve survival in patients with newly diagnosed glioblastoma
- To evaluate the safety and tolerability of ipilimumab plus temozolomide vs. temozolomide alone.
To evaluate whether the addition of ipilimumab to the current standard of care following surgery and radiotherapy will improve survival in patients with newly diagnosed glioblastoma in the long-term.
- To evaluate whether the addition of ipilimumab to the current standard of care following surgery and radiotherapy will improve long term progression-free survival in patients with newly diagnosed glioblastoma.
- Newly diagnosed histologically-confirmed de-novo supratentorial glioblastoma (including gliosarcoma), by WHO guidelines with >20% surgical debulking (surgeon defined).
- Radiotherapy to have begun within 49 days of surgery.
- Completed standard radiotherapy and concurrent temozolomide.
- Clinically appropriate for adjuvant temozolomide, and capable of completing adjuvant temozolomide without dose reduction, based on investigator judgement.
- Male or female, age 18-70 years.
- Life expectancy of at least 12 weeks.
- ECOG performance status of 0-1
- The patient is willing and able to comply with the protocol scheduled follow-up visits and examinations for the duration of the study.
- Written (signed and dated) informed consent.
- Haematological and biochemical indices within the ranges shown below:
≥9 g/dL (blood transfusions not permitted to maintain haemoglobin)
≥100 x 109/L
Absolute Neutrophil Count
≥1.0 x 109/L (G-CSF not permitted to maintain ANC)
≥0.5 x 109/L
< 1.5 x ULN or a creatinine clearance of ≥ 50mL/min calculated by Cockcroft-Gault formula
≤ 1.5 x ULN (except for patients with known Gilbert’s Syndrome who may have total bilirubin ≤ 3 x ULN)
ALT and AST
≤ 3 x ULN
- Pregnant or breast-feeding women or women of childbearing potential unless effective methods of contraception are used.
- Males not willing to agree with contraception advice (see Protocol Section 5.1).
- Multifocal glioblastoma.
- Secondary glioblastoma (i.e. previous histological or radiological diagnosis of lower grade glioma).
- Known extracranial metastatic or leptomeningeal disease.
- Any treatment for glioblastoma other than surgery and temozolomide chemoradiotherapy.
- Dexamethasone dose >3mg daily (or equivalent) at time of randomisation.
- Intratumoural or peritumoural haemorrhage deemed significant by the treating physician.
- Clinically relevant, active, known or suspected autoimmune disease.
- History of significant gastrointestinal impairment, as judged by the investigator.
- Any evidence of severe or uncontrolled diseases (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease).
- Serious and opportunistic infection within 4 weeks of screening.
- Known hypersensitivity to trial medications or any of their excipients e.g. hypersensitivity to dacarbazine (DTIC), patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glycose-galactose malabsorption.
- Past medical history of interstitial lung disease, idiopathic pulmonary fibrosis, drug-induced interstitial disease which required steroid treatment or any evidence of clinically active interstitial lung disease.
- Any condition requiring systemic treatment with corticosteroids dexamethasone 3mg or equivalent) or other immunosuppressive medications within 14 days or randomisation. Inhaled or topical steroids, and adrenal replacement steroid doses > 10mg daily prednisolone or equivalent are permitted in the absence of active autoimmune disease.
- Treatment with any other investigational agent, or participation in another interventional clinical trial (on the interventional arm) within 28 days prior to enrolment. Participation in other interventional trials after the final IPI-GLIO visit is permitted
- Any other active malignancy requiring treatment/whose prognosis will prevent readout from trial-endpoints -, exceptions include adequately treated cone-biopsied in situ carcinoma of the cervix uteri and non-melanoma skin lesions.
- Patients with a known history or who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
- Other psychological, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results.
Funding: The study is funded by Bristol Myers-Squibb and The National Brain Appeal.
For details of participating hospitals and consultants responsible for the trial locally, there is a list provided at the top of this page.
As we administer clinical research studies we are unable to offer medical advice relating to individual patient care.
For other queries:
Tel: +44 (0)1865 617 083 / (0)1865 617 080