A Randomised Phase II Study of NivolUmab and TeMozolomide vs Temozolomide Alone in Newly Diagnosed Elderly Patients With Glioblastoma (NUTMEG)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 103
- 试验地点
- 20
- 主要终点
- Overall survival outcomes
研究概览
简要总结
This study aims to investigate effect of Nivolumab and Temozolomide vs Temozolomide alone on overall survival in newly diagnosed elderly patients with glioblastoma.
Who is it for? You may be eligible to join this study if you are aged 65 years or above, with newly diagnosed histologically confirmed GBM (WHO grade IV glioma including gliosarcoma) following surgery.
The study aims to evaluate whether the combination of adjuvant nivolumab with temozolomide improves overall survival outcomes for this patient population. The outcome of the study will help determine the most effective treatment for patients with glioblastoma in the future.
详细描述
Study details:
Participants will be allocated to either experimental or control group in a 2:1 ratio by chance (randomly). Patients assigned to the experimental group will receive a course of nivolumab via intravenous infusion (240 mg on days 1 and 15 every 28 days for cycles 1-4; then 480 mg day 1 every 28 days for cycles 5-6) in addition to the standard regimen of Temozolomide (TMZ) tablets and radiotherapy. Patients assigned to the control group will receive the standard treatment of adjuvant temozolomide (150-200mg/m2 days 1-5 every 28 days) for 6 cycles and standard radiotherapy treatment (40 Gy administered in 15 fractions).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults, aged greater than or equal to 70 years, or aged 65-69 years if long course RT is inappropriate, with newly diagnosed histologically confirmed GBM (WHO grade IV glioma including gliosarcoma) following surgery
- •Tissue available for MGMT testing
- •Life expectancy of >12 weeks
- •Adequate bone marrow function (platelets > 100 x 10^9/L, ANC > 1.5 x 10^9/L)
- •Adequate liver function (ALT/AST < 1.5 x ULN)
- •Adequate renal function (creatinine clearance > 30 ml/min measured using Cockcroft-Gault
- •Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments including MRI
- •Signed, written informed consent
排除标准
- •Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may impact with the administration of study related treatments or procedures
- •Other co-morbidities or conditions that may compromise assessment of key outcomes
- •Prior chemotherapy or cranial radiation within the last 5 years. Prior or concomitant therapies for GBM (except surgery).
- •History of another malignancy within 2 years prior to registration. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 2 years after definitive primary treatment.
- •Significant infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated
- •Active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- •For symptoms related to GBM, the need for >4 mg/day of dexamethasone or >20 mg/day prednisone (or equivalent) at the time of screening.
- •For a condition other than GBM, the need for >2 mg/day of dexamethasone or >10 mg/day prednisone (or equivalent) or other immunosuppressive medications within 14 days prior to randomisation. Exceptions to this include the use of inhaled or topical steroids >10 mg/day prednisone (or equivalent), which are permitted in the absence of active autoimmune disease.
研究组 & 干预措施
Nivolumab and Temozolomide
After radiotherapy and 4 week break, participants who are assigned to this arm will receive Nivolumab with concurrent adjuvant temozolomide treatment
干预措施: Nivolumab (Drug)
Nivolumab and Temozolomide
After radiotherapy and 4 week break, participants who are assigned to this arm will receive Nivolumab with concurrent adjuvant temozolomide treatment
干预措施: Temozolomide (Drug)
Temozolomide
After radiotherapy and 4 week break, participants who are assigned to this arm will receive the standard treatment of adjuvant temozolomide treatment
干预措施: Temozolomide (Drug)
结局指标
主要结局
Overall survival outcomes
时间窗: 24 months post randomisation of first participant
Overall survival is defined as the interval from the date of randomisation to date of death from any cause, or date of last known follow-up alive. This will be calculated using the Kaplan-Meier method.
次要结局
- Health related quality of life of participants (EuroQoL EQ-5D-5L)(Through study completion, up to 24 months)
- Correlating modified RANO and immune related RANO in the experimental arm(Through study completion, up to 24 months)
- Progression Free Survival(6 months post randomisation)
- Number and severity of adverse events(Through study completion, up to 24 months)
- Health related quality of life of participants (QLQ C-30)(Through study completion, up to 24 months)
- Neurologic function of participants(Through study completion, up to 24 months)
- Health related quality of life of participants (QLQ-BN20)(Through study completion, up to 24 months)