Full Title: 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
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
Mount Vernon Cancer Centre, Northwood
Addenbrookes Hospital, Cambridge
Western General Hospital, Edinburgh
Guy’s Hospital, London
University College London Hospitals, London
Sites in Set-Up
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:
|Lab Test||Value Required|
|Haemoglobin (Hb)||≥9 g/dL (blood transfusions not permitted to maintain haemoglobin)|
|Platelet count||≥100 x 109/L|
|Absolute Neutrophil Count||≥1.0 x 109/L (G-CSF not permitted to maintain ANC)|
|Lymphocyte count||≥0.5 x 109/L|
|Serum creatinine||< 1.5 x ULN or a creatinine clearance of ≥ 50mL/min calculated by Cockcroft-Gault formula|
|Total bilirubin||≤ 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.