Condition category
Cancer
Date applied
12/11/2018
Date assigned
12/11/2018
Last edited
12/11/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Lay summary under review with external organisation

Trial website

http://www.oncology.ox.ac.uk/trial/ipi-glio

Contact information

Type

Scientific

Primary contact

Ms Stasya Ng

ORCID ID

Contact details

Oncology Clinical Trials Office
Department of Oncology
Old Road Campus Research Building
Roosevelt Drive
Headington
Oxford
OX3 7DQ
United Kingdom
+44 (0)1865 617083
octo-ipiglio@oncology.ox.ac.uk

Additional identifiers

EudraCT number

2018-000095-15

ClinicalTrials.gov number

Protocol/serial number

37562

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)

Acronym

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

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

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

Intervention

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

Drug

Phase

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

10/01/2018

Overall trial end date

07/06/2026

Reason abandoned (if study stopped)

Eligibility

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

Patient

Age group

Adult

Gender

Both

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

07/12/2018

Recruitment end date

07/06/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

-
-
United Kingdom

Sponsor information

Organisation

University of Oxford

Sponsor details

Clinical Trials & Research Governance
Joint Research Office
Boundary Brook House
Headington
Oxford
OX3 7GB
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Industry

Funder name

Bristol-Myers Squibb

Alternative name(s)

Bristol-Myers Squibb Company, BMS

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United States of America

Funder name

University College London Hospitals Charities; Grant Codes: H3R00532.H300.03

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The National Hospital for Neurology and Neurosurgery Development Foundation; Grant Codes: NBA/IpiGlio

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

07/06/2027

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes