Phase I/II Study of AGuIX Nanoparticles with Radiotherapy Plus Concomitant Temozolomide in the Treatment of Newly Diagnosed Glioblastoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 66
- 试验地点
- 9
- 主要终点
- 6-month Progression Free Survival (PFS) rate (phase II)
研究概览
简要总结
This is a phase I/II clinical trial evaluating the association of AGuIX nanoparticles with radiotherapy plus concomitant Temozolomide in the treatment of newly diagnosed glioblastoma.
The primary objectives of this study were to determine the recommended dose of AGuIX in combination with radiotherapy and TMZ during the concomitant radiochemotherapy period (phase I) and to estimate the efficacy of the combination radiochemotherapy + AGuIX (recommended dose), measured by the 6-month progression-free survival rate (PFS) (phase II)
Three dose levels of intravenous AGuIX nanoparticles will be explored: 50 mg/kg, 75 mg/kg and 100 mg/kg.
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological diagnosis of grade IV glioblastoma (biopsy or partial surgery)
- •Patient not operated or partial resection
- •KPS superior to 70%
- •Age between 18 years old and 75 years old
- •Life expectancy superior to 6 months
- •Platelets superior to 100,000 / mm3
- •PNN superior to 1500 / mm3
- •Hb superior to 10 g / dL
- •Creatinine superior to 1.5 times the upper normal limit or clearance according to Cockcroft-Gault superior to 50 mL / min
- •Liver function (GGT, PAL, ASAT, ALAT, bilirubin) superior to 1.5 times the upper normal limit
- •For patients receiving treatment with corticosteroids, treatment with corticosteroids must be at a stable or decreasing dose for at least 14 days before inclusion
- •Patient able to swallow and retain oral medication
- •Negative serum pregnancy test within 7 days before the first administration of treatment for women
- •Women of childbearing potential and men whose partners are of childbearing potential must agree to use, themselves or their partners, an approved method of contraception throughout the treatment and at least 6 months after the last administration of study treatment.
- •Obtaining signed informed consent from the patient
- •Patient affiliated to a social security regimen
排除标准
- •prior brain radiotherapy
- •prior chemotherapy (including implants containing carmustine (Gliadel®) or immunotherapy (vaccination included)
- •Any contraindication to TMZ listed in the SPCs
- •History of major intestinal resection which may modify the absorption of oral drugs according to the judgment of the investigator
- •Diagnosed inflammatory bowel disease (Crohn disease or ulcerative colitis)
- •Diarrhea superior to grade 2 CTCAE (whatever the cause)
- •Current or recent treatment with another investigational drug or participation in another therapeutic clinical trial (within 30 days of inclusion).
- •History of other cancer in the 5 years preceding inclusion, except for basal cell carcinomas of the skin and in situ carcinomas of the cervix
- •Pregnant or breastfeeding women
- •Contraindication to MRI or gadolinium injection
- •History of severe anaphylactic reactions due to the injection of gadolinium-based contrast product (dotarem, etc.)
- •Patient under guardianship or curatorship
- •History of nephropathy
- •Psychological disorder or social or geographic reasons that may compromise medical monitoring of the trial or compliance with treatment
研究组 & 干预措施
AGuIX + chemoradiotherapy (radiotherapy + temozolomide)
addition of AGuIX nanoparticles to standard radiotherapy and concomitant treatment by temozolomide (TMZ) for patients of phase I and patients randomized in experimental arm of phase II
干预措施: Polysiloxane Gd-Chelates based nanoparticles (AGuIX) (Drug)
AGuIX + chemoradiotherapy (radiotherapy + temozolomide)
addition of AGuIX nanoparticles to standard radiotherapy and concomitant treatment by temozolomide (TMZ) for patients of phase I and patients randomized in experimental arm of phase II
干预措施: radiotherapy (Radiation)
AGuIX + chemoradiotherapy (radiotherapy + temozolomide)
addition of AGuIX nanoparticles to standard radiotherapy and concomitant treatment by temozolomide (TMZ) for patients of phase I and patients randomized in experimental arm of phase II
干预措施: Temozolomide (Drug)
chemoradiotherapy (radiotherapy + temozolomide)
standard of care : chemoradiotherapy (radiotherapy + temozolomide) for patients randomized in control arm of phase II
干预措施: radiotherapy (Radiation)
chemoradiotherapy (radiotherapy + temozolomide)
standard of care : chemoradiotherapy (radiotherapy + temozolomide) for patients randomized in control arm of phase II
干预措施: Temozolomide (Drug)
结局指标
主要结局
6-month Progression Free Survival (PFS) rate (phase II)
时间窗: 6 months from the start of treatment
The recommended dose (phase I) of AGuIX in combination with TMZ and and radiotherapy during the radio-chemotherapy period
时间窗: during 6 weeks after the first injection of AGuIX
Only toxicities occurring during concomitant radiochemotherapy will be considered for the evaluation of Dose Limiting Toxicity radiotherapy during the radio-chemotherapy period is defined as the highest dose tested in which the % of dose-limiting toxicities (DLT) is less than 33%. DLT is defined as any grade 3-4 toxicity according to the NCI CTCAE v5.0 classification, except alopecia, nausea, and vomiting which can be quickly controlled with appropriate measures.
次要结局
- Overall Survival(from the start of treatment to death, up to 24 months)
- Progression Free Survival (PFS)(from the start of treatment to progression, up to 24 months)
- Pharmacokinetic Tmax of AGuIX(Day 0 , Day 7, Day 14)
- distribution of AGuIX(after the first and last injection of AGuIX, Week 0 and Day 14)
- Pharmacokinetic Cmax of AGuIX(Day 0 , Day 7, Day 14)
- Pharmacokinetic AUC of AGuIX(Day 0 , Day 7, Day 14)
- Pharmacokinetic t1/2 of AGuIX(Day 0 , Day 7, Day 14)
- Toxicity (CTCAE criteria)(from baseline to 30 days after treatment (concomitant and adjuvant treatment) (week 35))