A Phase II, Open Label, Randomised Study of Ipilimumab with Temozolomide versus Temozolomide alone after surgery and chemoradiotherapy in patients with recently diagnosed glioblastoma
- Conditions
- GlioblastomaMedDRA version: 20.0Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000095-15-GB
- Lead Sponsor
- niversity of Oxford
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 120
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.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 113
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 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.;Secondary Objective: To evaluate the safety and tolerability of ipilimumab plus temozolomide vs temozolomide alone.<br>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.;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.<br>;Timepoint(s) of evaluation of this end point: 18 months from the date the last participant is randomised.<br>
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Toxicity grade =3 graded according to CTCAE v4.03 and length of time for toxicity to resolve. <br><br>Overall survival at 5 years including a treatment effect reported as a hazard ratio;Timepoint(s) of evaluation of this end point: Throughout study from start of treatment with IMP until 52 week end of study visit.<br><br>Up to a maximum of 5 years from individual participant randomisation