Trial of ipilimumab immunotherapy in recently diagnosed glioblastoma brain tumours

Phase 2

Completed

• Conditions: Cancer; Glioblastoma

• Registration Number: ISRCTN84434175
• Lead Sponsor: niversity of Oxford

Brief Summary

2020 Protocol article in https://pubmed.ncbi.nlm.nih.gov/32164579/ protocol (added 24/04/2023)

Detailed Description

Not available

Study Timeline

• Study Start: 2018-11-12
• Study Completion: 2022-10-31
• Last Update Posted: 22 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 119

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 < 1.5 x ULN or a creatinine clearance of = 50mL/min calculated by Cockcroft-Gault formula
Female CrCl = (140-age in years) x weight in kg x 1.04 serum creatinine in µmol/L
Male CrCl = (140-age in years) x weight in kg x 1.23 serum creatinine in µmol/L
Total bilirubin = 1.5 x ULN (except for patients with known Gilbert’s Syndrome who may have total bilirubin = 3 x ULN)
ALT and AST = 3 x ULN

Previous participant inclusion criteria as of 17/10/2019:
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

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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified