E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Glioblastoma is a type of brain cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018336 |
E.1.2 | Term | Glioblastoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Information not present in EudraCT |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 and concurrent temozolomide. 4. Clinically appropriate for adjuvant temozolomide and capable of completing adjuvant temozolomide without dose reduction, based on investigator judgement. 5. Male or female, age 18-70 years. 6. Life expectancy of at least 12 weeks. 7. ECOG performance status of 0-1 8. The patient is willing and able to comply with the protocol scheduled follow-up visits and examinations for the duration of the study. 9. Written (signed and dated) informed consent. 10. Haematological and biochemical indices within stated ranges.
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E.4 | Principal exclusion criteria |
1. Pregnant or breast-feeding 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival. 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.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
18 months from the date the last participant is randomised.
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E.5.2 | Secondary end point(s) |
Toxicity grade ≥3 graded according to CTCAE v4.03 and length of time for toxicity to resolve.
Overall survival at 5 years including a treatment effect reported as a hazard ratio |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout study from start of treatment with IMP until 52 week end of study visit.
Up to a maximum of 5 years from individual participant randomisation |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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For this study, the LVLS will be 52 weeks post randomisation. However, this will be followed by collection of survival data and other information relevant to survival from medical records, which will continue for a maximum of five years after individual participant randomisation, or when all participants have died (whichever comes first). For the purposes of the Research Ethics Committee (REC) and regulatory authority approval, the trial end date is deemed to be the date of last data capture. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 30 |