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 5-7 sites in the UK.
Target Opening to Recruitment: 21 December 2018
- 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.