Condition category
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status

Contact information



Primary contact

Ms Stasya Ng


Contact details

Oncology Clinical Trials Office
Department of Oncology
Old Road Campus Research Building
Roosevelt Drive
United Kingdom
+44 (0)1865 617083



Additional contact

Dr Paul Mulholland


Contact details

University College London Hospitals
250 Euston Road
United Kingdom

Additional identifiers

EudraCT number

2018-000095-15 number

Protocol/serial number


Study information

Scientific 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 (IPI-GLIO)



Study hypothesis

Glioblastoma is the most common malignant primary brain tumour. The trialists are trying to find out whether after chemoradiotherapy it is better to continue with standard treatment with temozolomide, or if adding a drug called ipilimumab to standard treatment is better in terms of survival and/or safety and tolerability. They hypothesise that adding ipilimumab to standard treatment is better.

Ethics approval

South Central – Oxford B Research Ethics Committee, 02/11/2018, ref: 18/SC/0525

Study design

Randomised; Interventional; Design type: Treatment, Drug, Immunotherapy

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet




This is an unblinded, open labelled stratified randomised Phase II multicentre clinical trial (CTIMP). Patients with newly diagnosed de-novo glioblastoma following surgery and radical radiotherapy with concomitant temozolomide will be recruited from 5-7 hospitals in the UK.

The study will have statistical power of 80% to show a significant difference between 22.5 month median survival in the ipilimumab and temozolomide arm and 15 month median survival in the temozolomide arm. To allow this, 120 patients need to be recruited (80 to the ipilimumab and temozolomide arm and 40 to the temozolomide arm) This assumes an 18 month recruitment period and survival follow-up for a minimum of 18 months after the last participant randomised (maximum of 5 years after individual participant randomisation). A 2:1 randomisation was chosen to aid recruitment and because there is already 10 years of experience of temozolomide in the public domain.

All analyses will be on an intention-to-treat basis. This means that patients will be analysed as they are randomised irrespective of the treatment actually received. The intention-to-treat population will include all patients who have given their informed consent and for whom there is confirmation of successful allocation of a randomisation number. It is therefore important that every effort is made to encourage patients, including those patients who do not receive/complete their allocated treatment, to attend for follow-up clinic visits to avoid bias in the analysis of the results. No interim analyses are planned.

Patients will be randomly allocated in a 2:1 ratio to receive either:
Arm A: ipilimumab + temozolomide, 80 patients
Arm B: temozolomide, 40 patients

Ipilimumab given by intravenous infusion at a dosage of 3mg/kg every 3 weeks for a total of 4 doses.

Temozolomide is taken orally for 6 cycles. Each cycle is 28 days long once daily for 5 days followed by 23 days without treatment. Patients take 150mg/m^2/day for Cycle 1 (Dose Level 0), and then 200mg/m^2/day (Dose Level 1) during Cycles 2-6 in the absence of toxicity except in cases as described in the protocol where it is taken at Dose Level -1. The dose may be reduced to 100 mg/m^2/day (Dose Level -1) in case of toxicity.

The duration of study treatment is 24 weeks and the end of study visit is at 52 weeks. Survival data and other information relevant to survival will be collected from medical records at 18 months from the last participant's randomisation and 2, 3, and 5 years from individual participant randomisation dates.

Intervention type



Phase II

Drug names

Ipilimumab, temozolomide

Primary outcome measure

Overall survival (OS). The treatment comparison will be reported as the hazard ratio (HR) plus 80% confidence interval. 18-month survival rates per treatment groups will be reported; Timepoint(s): 18 months from the last patient's randomisation

Secondary outcome measures

1. Any toxicity grade ≥3 graded according to CTCAE v4.03 and length of time for toxicity to resolve; Timepoint(s): From the time of patient consent until patient's end of study
2. Overall survival at 5 years including a treatment effect reported as a hazard ratio; Timepoint(s): 5 years from the patient's randomisation date

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Newly diagnosed histologically-confirmed de-novo supratentorial glioblastoma (including gliosarcoma), by WHO guidelines with >20% surgical debulking (surgeon defined)
2. Radiotherapy to have begun within 49 days of surgery
3. Completed standard radiotherapy (60 Gray in 30 Fractions) given with concurrent temozolomide
4. Completed all planned concomitant temozolomide (75mg/m2 for 42 days) in combination with radiotherapy
5. Clinically appropriate for adjuvant temozolomide, based on investigator judgement
6. Male or female, age 18-70 years
7. Life expectancy of at least 12 weeks
8. ECOG performance status of 0-1
9. The patient is willing and able to comply with the protocol scheduled follow-up visits and examinations for the duration of the study
10. Written (signed and dated) informed consent
11. Haematological and biochemical indices within stated ranges

Participant type


Age group




Target number of participants

Planned Sample Size: 120; UK Sample Size: 120

Participant exclusion criteria

1. Pregnant or breastfeeding women or women of childbearing potential unless effective methods of contraception are used
2. Multifocal glioblastoma
3. Secondary glioblastoma (i.e. previous histological or radiological diagnosis of lower grade glioma)
4. Known extracranial metastatic or leptomeningeal disease
5. Any treatment for glioblastoma other than surgical resection/biopsy and temozolomide chemoradiotherapy
6. Dexamethasone dose > 3mg daily (or equivalent) at time of randomisation
7. Intratumoural or peritumoural haemorrhage deemed significant by the treating physician
8. Clinically relevant, active, known or suspected autoimmune disease
9. History of significant gastrointestinal impairment, as judged by the investigator
10. Any evidence of severe or uncontrolled diseases (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease)
11. Known hypersensitivity to trial medications or any of their excipients
12. 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
13. 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

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Mount Vernon Cancer Centre
Mount Vernon Hospital Rickmansworth Rd
United Kingdom

Trial participating centre

Western General Hospital
Edinburgh Cancer Centre Crewe Road South
United Kingdom

Trial participating centre

Addenbrookes Hospital
Hills Rd
United Kingdom

Trial participating centre

Guy’s Hospital
Great Maze Pond
United Kingdom

Trial participating centre

Churchill Hospital
Old Road
United Kingdom

Trial participating centre

University College London Hospitals NHS Foundation Trust
250 Euston Road
United Kingdom

Trial participating centre

The Christie
Wilmslow Road
M20 4BX
United Kingdom

Sponsor information


University of Oxford

Sponsor details

Clinical Trials & Research Governance
Joint Research Office
Boundary Brook House
United Kingdom

Sponsor type




Funder type


Funder name

Bristol-Myers Squibb

Alternative name(s)

Bristol-Myers Squibb Company, BMS

Funding Body Type

private sector organisation

Funding Body Subtype

For-profit companies (industry)


United States of America

Funder name

The National Brain Appeal

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date


Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

11/04/2019: The Christie was added to the trial participating centres. 25/03/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Brain Cancer; Health Category: Cancer and neoplasms; Disease/Condition: Malignant neoplasms of eye, brain and other parts of central nervous system" to "Glioblastoma" following a request from the NIHR. 05/03/2019: Internal review. 20/02/2019: Funders updated: The National Hospital for Neurology and Neurosurgery Development Foundation was replaced with The National Brain Appeal. 19/02/2019: Cancer Research UK lay summary link added to plain English summary field. 19/02/2019: The following changes were made to the trial record: 1. Churchill Hospital and University College London Hospitals NHS Foundation Trust were added as trial participating centres. 2. The recruitment end date was changed from 07/06/2020 to 21/06/2020. 06/02/2019: New contact added. 25/01/2019: University College London Hospitals Charities was removed from the funders - this was added in error. 27/12/2018: Guy’s Hospital, Addenbrookes Hospital and Western General Hospital have been added to the trial participating centres 21/12/2018: The following changes have been made: 1. The recruitment start date has been changed from 07/12/2018 to 21/12/2018. 2. Mount Vernon Cancer Centre has been added to the trial participating centres.