Strategic treatment Pause of first-line Immune Check point inhibitor + Inhibitor in good or only one adverse prognostic factor in intermediate risk metastatic renal cell carcinoma (mRCC) with an objective response: a randomized, non-inferiority phase III study - SPICI
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 372
- 试验地点
- 24
- 主要终点
- Percentage of participants without progression at up to 12 months after randomisation, based on a blinded independent central review (BICR) according to RECIST v1.1 criteria
研究概览
简要总结
To assess the non-inferiority of treatment pause compared to treatment continuation with PD-1/ PDL-L1 ICIs + VEGFR-Tyrosine Kinase inhibitor in an IMDC good risk or only one adverse prognostic factor intermediate risk mRCC population that has achieved an objective response between the end of the 11th month and the end of the 13th of treatment with the combination regimens
详细描述
Although multiple combinations therapies in particular PD-1/PD-L1 immune-checkpoint inhibitors (PD-1/PD-L1 ICIs) in combination with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) are approved and have improved patient's outcomes with mRCC, they are maintained until disease progression and treatment pause after an objective response has not been fully explored [5-7]. The good-risk population is characterised by prolonged survival therefore a treatment pause in this population could impact the quality of life, safety and total cost of care, without impacting outcome. As well, intermediate risk population group is heterogeneous, while the one's with only one adverse prognostic factor seems to be closed to the outcome of good risk population [11-15]. As the purpose of the study is to target patients with an objective response, there is already a selection of patients with a better outcome.
Patient will be randomised after 11 to 13 months of treatment with PD-1/PD-L1 ICI plus VEGFR-TKI (treatment pause versus treatment continuation) and follow every 3 months for a period of 12 months following by 12 additional months for survival follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Arm B (control arm): treatment continuation
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Age ≥ 18 years at time of signing informed consent form
- •Karnofsky Performance Status (KPS) grade ≥ 70%
- •Measurable disease as per RECIST v1.1 per investigator on CT scan at the initiation of first line treatment with combination treatment with PD-1/PD-L1 ICI and VEGFR-TKI
- •Adequate organ function
- •Females of childbearing potential must use a highly effective contraception (combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral ; intravaginal ;transdermal) ; progestogen-only hormonal contraception associated with inhibition of ovulation (oral ; injectable ; implantable ; intrauterine device (IUD) ; intrauterine hormone-releasing system ( IUS)) ; bilateral tubal occlusion ; vasectomised partner ; sexual abstinence) and continue its use for 5 months after the last PD1/PD L1 ICI administration
- •Sexually active male patients must agree to use condoms and continue its use for 5 months after the last PD1/PD L1 ICI administration
- •Willingness and ability to comply with study procedures
- •Patient affiliated to a social security system or benefit from the same system
- •Signed informed consent form
- •Histological confirmation of RCC with a Clear-cell component, including subject who also have a sarcomatoïd feature
- •Advanced (not amenable to curative surgery or radiation therapy) or Metastatic RCC (American Joint Committee on Cancer [AJCC] Stage IV)
- •Participants with good or intermediate risk with only one adverse prognostic factor will be eligible as per International Metastatic RCC Database Consortium (IMDC) criteria
- •Prior first line therapy for mRCC with the combination of PD-1/ PD-L1 ICI plus VEGFR-TKI
- •First line treatment with the combination of PD-1/PD-L1 ICI and VEGFR-TKI must be ongoing whatever the dose with no period of discontinuation > 6 consecutive weeks during treatment of the PD-1/PD-L1 ICI, and 2 consecutive weeks in the last 3 months before randomisation for the VEGFR-TKI
- •Patients with an objective response (complete response or partial response) between the end of the 11th month and the end of the 13th month of the combination treatment with PD-1/PD-L1 ICI and VEGFR-TKI
- •CT scan at the initiation of this treatment must be available
排除标准
- •Prior therapy with PD-1/PD-L1 ICI or VEGFR-TKI monotherapy
- •Poorly controlled hypertension despite antihypertensive therapy
- •More than one adverse prognostic factor (IMDC criteria)
- •Women who are pregnant or lactating
- •Current participation in an investigational program
- •Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study
- •Adults who are the subject of legal protection measures
- •Persons deprived of their liberty by a judicial or administrative decision
结局指标
主要结局
Percentage of participants without progression at up to 12 months after randomisation, based on a blinded independent central review (BICR) according to RECIST v1.1 criteria
Percentage of participants without progression at up to 12 months after randomisation, based on a blinded independent central review (BICR) according to RECIST v1.1 criteria
次要结局
- Proportion of participants who experience an adverse event or serious adverse event, and mean number of adverse events or serious adverse events up to 12 months after randomisation
- Mean change in quality of life up to 12 months after randomisation, measured by the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI-19)
- Mean scores in the Hospital Anxiety and Depression Scale at up to 12 months after randomisation
- Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST)
- 2-year overall survival
- 2-year progression-free survival
- For patients in the experimental arm, site and distribution of the sites of progression: known lesions, new lesion(s) or both
- For patients in the experimental arm, distribution of treatment modality after progression: surveillance, focal treatment or general treatment
- For patients in the experimental arm, if general treatment when restarting PD-1/PD-L1 ICI + VEGFR-TKI, percentage of patients with status SD or in objective response at 6 months
- In France only, healthcare resource utilisation up to 12 months after randomisation, measured by medication use and hospitalisations
研究者
Coordinating Investigator
Scientific
Centre Hospitalier Universitaire De Bordeaux