A Phase II Trial of Neoadjuvant Therapy in Patients With Newly Diagnosed Glioblastoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 4
- 主要终点
- Survival rate at 24 months
研究概览
简要总结
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.
详细描述
This is a phase II trial to 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.
The trial will recruit 43 patients over 1 year.
Trial Subjects (patients) with newly diagnosed de-novo glioblastoma who are deemed eligible for the trial will be recruited to the study to receive neoadjuvant ipilimumab. Patients will receive 2 cycles of ipilimumab, administered intravenously at a dose of 3mg/kg on day 1 of each 21 day cycle.
Prior to trial entry the patient's treating multidisciplinary team (MDT) consisting of oncologists, radiologists and surgeons must agree that the patient is a suitable candidate for ipilimumab prior to surgery and that surgery may be delayed beyond usual standard of care timelines.
Patients will be assessed on a weekly basis, and disease assessments (including MRI scans) will be performed after each cycle of ipilimumab. Patient responses and associated MRI scans will be reviewed by the MDT to determine that it is safe for the patient to continue with trial treatment. On completion of trial treatment patients will have a further disease assessment (including MRI scan) which will be reviewed with the MDT before continuing to standard of care treatment of debulking surgery and chemoradiation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •Treatment with any other investigational agent within 28 days prior to starting study 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 deoxyribonucleic acid (DNA) test is negative and patients are willing to undergo monthly monitoring for Hepatitis B virus reactivation
- •Positive serology for Hepatitis C defined as a positive test for Hepatitis C virus 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
研究组 & 干预措施
Ipilimumab
3mg/kg Ipilimumab IV infusion (day 1) given as a 21 day cycle for 2 cycles.
干预措施: Ipilimumab (Drug)
结局指标
主要结局
Survival rate at 24 months
时间窗: 24 months after diagnostic biopsy
Number of patients alive at 24 months
次要结局
- Survival rate at 12 months(12 months after diagnostic biopsy)
- Resection rate(At the time of surgery)
- Best Overall Objective Response Rate(After ipilimumab treatment through to study completion, an average of 36 months)
- Time to treatment failure(1st diagnostic biopsy to early treatment discontinuation, progression, starting further treatment or death up to 24 months)
- Changes in Performance Status(From screening through to study completion, an average of 3 years)
- 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)
- Surgical complications(From surgery through to study completion, an average of 3 years)