A Study Assessing if it is Safe and Possible to Treat Brain Cancer Patients With Immunotherapy Before They Receive the Standard Treatment.

Official title

Window Studies in Glioblastoma: A Phase I Trial Investigating Neoadjuvant Ipilimumab in Newly Diagnosed Glioblastoma

Overview

WinGlio is a phase I study investigating neoadjuvant (before surgery) ipilimumab ( a type of immunotherapy drug) in patients with newly diagnosed glioblastoma (a form of brain cancer). Participants will receive up to 2 cycles of ipilimumab prior to the standard of care treatments for this patient group which can include debulking surgery and chemoradiation. The aim of giving the ipilimumab to the participants is to see if it is safe to treat patients with this condition with ipilimumab and also to see if the drug helps to reduce or control the patient's disease.

Interventions

• Biological Ipilimumab (3 mg/kg)
  All participants will be treated with ipilimumab (3mg/kg) for up to 2 cycles. Each cycle will last 21 days with participants receiving ipilimumab on the 1st day of the cycle.

Primary outcome measures

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [Time frame: From trial registration to 3 months post ipilimumab administration]
• Overall Survival at 12 months post trial registration [Time frame: From trial registration to 1 year post treatment]
• Feasibility of neoadjuvant ipilimumab [Time frame: Upon the final patient completing treatment]
• Best overall objective response rate [Time frame: Through study completion, an average of 14 months]

Secondary outcome measures (10)

• Overall survival at 24 months [Time frame: From date of registration up to 104 weeks]
• Progression Free Survival [Time frame: From date of registration up to date of progression]
• Surgical Complications [Time frame: During surgery]
• Treatment Compliance [Time frame: Through treatment completion, an average of 42 days]
• Changes in Eastern Cooperative Oncology Group performance status [Time frame: From baseline to end of 12 month follow up]
• Resection Rate [Time frame: postprocedural]
• Patient Acceptability [Time frame: Through treatment completion, average of 42 days]
• Surgeon Acceptability [Time frame: Baseline]
• Delay in Surgery [Time frame: Date of registration to date of surgery]
• Changes in Health Related Quality of Life (HRQoL) as measure by EORTC QLQ-C30 and QLQ-BN20 [Time frame: Screening to 3 month follow up]

Eligibility criteria

Inclusion criteria

• Radiologically or histologically confirmed, newly diagnosed de-novo supratentorial glioblastoma (including gliosarcoma)
• Age ≥18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see appendix 3)
• Clinically fit for, and appropriate to receive, neoadjuvant ipilimumab followed by standard of care treatment, based on investigator and MDT judgement
• Adequate organ and bone marrow function:

• Hb ≥9 g/dL
• Neutrophils ≥1.5 x 109/L
• Platelets ≥100 x 109/L
• Lymphocyte count ≥1.0 x 109/L
• Adequate renal function:

• Creatinine clearance of ≥ 50mL/min calculated by Cockroft-Gault equation
• Adequate liver function:

• Bilirubin ≤ 1.5 x ULN (except for patients with known Gilbert's Syndrome who may have total bilirubin ≤ 3 x ULN)
• Aspartate or alanine transferase (AST or ALT) ≤ 2.5 x ULN
• Life expectancy of greater than 12 weeks
• Willing to comply with the contraceptive requirements of the trial (see section 6.3.5)
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
• Written informed consent

Exclusion criteria

• Known extracranial metastatic or leptomeningeal disease
• Prior treatment for glioblastoma other than a biopsy or limited resection leaving residual disease
• Dexamethasone dose >3mg daily (or equivalent) at the time of starting study treatment
• Antibiotics received within 30 days prior to starting study treatment, except for prophylactic antibiotics given with surgery
• Intratumoural or peritumoural haemorrhage deemed significant by the treating clinician
• Active autoimmune disease apart from:

• Skin conditions such as psoriasis, vitiligo or alopecia not requiring systemic treatment
• Type 1 diabetes or thyroid disease, controlled on medication
• Any evidence of severe or uncontrolled diseases (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease)
• Known hypersensitivity to ipilimumab or any of its excipients
• 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.
• Any condition requiring systemic treatment with corticosteroids (>10mg prednisolone daily or equivalent) or other immunosuppressive medications within 14 days prior to starting study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10mg daily prednisolone or equivalent are permitted in the absence of active autoimmune disease.
• Treatment with any other investigational agent within 28 days or 5 half lives of the investigational agent (whichever is longer) prior to starting ipilimumab treatment.
• History of previous cancer within 5 years, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and non-melanoma skin lesions
• Positive serology for Hepatitis B defined as a positive test for HepB surface antigen (HBsAg). Note: patients who are HepB core antibody (HBcAb) positive will only be eligible for the study if the HepB virus deocyribonucleic acid (DNA) test is negative and patients are willing to undergo monthly monitoring for HBV reactivation.
• Positive serology for Hepatitis C defined as a positive test for HCV antibody
• Diagnosis of prior immunodeficiency or organ-transplant requiring immunosuppressive therapy or known HIV or acquired immunodeficiency syndrome (AIDS)-related illness
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Women who are pregnant or breast feeding

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United Kingdom · 1 center

• University College London Hospital — London

Identifiers

NCT: NCT07134842 · UCL/176169

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗