Glioblastoma Cancer
Conditions
Interventions
Current interventions as of 07/06/2021:
This is an unblinded, open labelled stratified randomised Phase II multicentre clinical trial (CTIMP). Patients with newly diagnosed de-novo glioblastoma follow
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 24/04/2023: 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 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 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 Previous 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
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 07/06/2021: 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 >3 mg 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 (dexamethasone 3 mg 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 14. Treatment with any other investigational agent, or participation in another interventional clinical trial (on the interventional arm) within 28 days prior to enrolment. Participation in other interventional trials after the final IPI-GLIO visit is permitted 15. Any other active malignancy requiring treatment/whose prognosis will prevent readout from trial-endpoints, exceptions include adequately treated cone-biopsied in situ carcinoma of the cervix uteri and non-melanoma skin lesions Previous 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 >3 mg 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 (>10 mg prednisolone daily or equivalent) or other immunosuppressive medications within 14 days or randomisation. Inhaled or topical steroids, and adrenal replacement steroid doses >10 mg daily prednisolone
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 07/06/2021: 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 3 years including a treatment effect reported as a hazard ratio; Timepoint(s): 3 years from the patient's randomisation date 4. Progression-free survival (PFS) measured at 18 months from 30th April 2021 Previous 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 | — |
Countries
England, Scotland, United Kingdom
Outcome results
None listed