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
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 or temozolomide alone.
Recruiting as of 21st Dec 2018
Target: 120 Patients
Arm A: 80 patients
Arm B: 40 patients
Mount Vernon Cancer Centre, Northwood
Addenbrooke's Hospital, Cambridge
Western General Hospital, Edinburgh
Guy’s Hospital, London
University College Hospital, London
Churchill Hospital, Oxford
The Christie, Manchester
- 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.
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- 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 (60 Gray in 30 Fractions) given with concurrent temozolomide.
- Completed all planned concomitant temozolomide (75mg/m2 for 42 days) in combination with radiotherapy.
- Clinically appropriate for adjuvant temozolomide, 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 (>10mg prednisolone daily 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 within 28 days prior to enrolment. Participation in other interventional trials after IPI-GLIO is permitted.
- Any other active malignancy, with the exception of 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.
If you are considering participation in the IPI-GLIO trial please contact your local hospital. We are unable to offer advice relating to individual patient care. For other queries:
Tel: +44 (0)1865 617 083 / (0)1865 617 080