A Trial of Neoadjuvant Therapy in Patients With Newly Diagnosed Glioblastoma

NCT05074992 | Terminated Phase 2 DMC

• 1 other identifier: UCL/134643
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 4

Brief Summary

The NeAT Glio trial will evaluate whether the addition of ipilimumab prior to the current standard treatment of surgery and chemoradiotherapy will improve survival in patients with newly diagnosed glioblastoma.

Conditions

Glioblastoma

Keywords

Newly Diagnosed

Outcome Measures

Primary Outcomes (1)

• Survival rate at 24 months

  Number of patients alive at 24 months

  24 months after diagnostic biopsy

Secondary Outcomes (8)

• Survival rate at 12 months

  12 months after diagnostic biopsy

• Time to treatment failure

  1st diagnostic biopsy to early treatment discontinuation, progression, starting further treatment or death up to 24 months

• Best Overall Objective Response Rate

  After ipilimumab treatment through to study completion, an average of 36 months

• Treatment emergent adverse events

  From start of treatment until 3 months post administration of ipilimumab

• Treatment Compliance

  From start of treatment until treatment discontinuation, an average of 2 months

Study Arms (1)

Ipilimumab

EXPERIMENTAL

3mg/kg Ipilimumab IV infusion (day 1) given as a 21 day cycle for 2 cycles.

Drug: Ipilimumab

Interventions

Ipilimumab DRUG

Ipilimumab is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed, newly diagnosed de-novo supratentorial glioblastoma (including gliosarcoma)
• Age ≥18 years
• Tumour deemed appropriate for surgical debulking
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• 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 ≥1.0 x 10 9/L, platelets ≥100 x 10 9/L and lymphocyte count ≥1.0 x 10 9/L
• Adequate renal function: \< 1.5 x ULN or a creatinine clearance of ≥ 50mL/min calculated by Cockroft-Gault equation
• Adequate liver function, including:
• 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
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
• Willing to donate tumour material and serial blood samples
• Written informed consent

You may not qualify if:

• Diagnosis of Multifocal glioblastoma (Multicentric glioblastoma permitted)
• Prior resection of glioblastoma leaving inadequate tissue for post investigational treatment resection
• Secondary glioblastoma (i.e. previous histological or radiological diagnosis of lower grade glioma)
• Known extracranial metastatic or leptomeningeal disease
• Prior treatment for glioblastoma other than a limited resection or biopsy
• Dexamethasone dose \>3mg daily (or equivalent) at the time of starting study treatment
• Antibiotics within 30 days of starting study treatment
• Intratumoural or peritumoural haemorrhage deemed significant by the treating physician
• 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 of 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

Sponsors & Collaborators

• University College, London: lead
• Bristol-Myers Squibb: collaborator

Study Sites (4)

Aberdeen Royal Infirmary

Aberdeen, United Kingdom

Location

St Bartholomew's Hospital

London, United Kingdom

Location

University College London Hospital

London, United Kingdom

Location

Queen's Hospital

Romford, United Kingdom

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Ipilimumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Paul Mulholland

  University College London Hospitals

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2021
• First Posted: October 12, 2021
• Study Start: August 24, 2022
• Primary Completion: May 2, 2023
• Study Completion: May 2, 2023
• Last Updated: May 2, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (4)