2024-520045-23-00招募中2 期
A Phase 2 BIOmarker driven trial with Nivolumab and Ipilimumab or VEGFR tKi in naïve metastatic Kidney cancer
ARTIC16 个研究点 分布在 1 个国家目标入组 200 人开始时间: 2025年1月30日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 16
- 主要终点
- Investigator-assessed ORR is defined as the proportion of randomized subjects who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) using RECIST 1.1 criteria based on Investigator assessments.
研究概览
简要总结
To evaluate the ORR according to molecular subgroups (ccRCC1 to 4)and assigned treatment (nivolumab monotherapy, nivolumab combined with ipilimumab, or TKI: sunitinib or pazopanib), based on Investigator assessments.
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Design of the study
- 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
- 否
入选标准
- •Histological confirmation of RCC with a clear-cell component. Patients with TFE3 or TFEB translocation proven by cytogenetic analysis or by fluorescence in situ hybridization (FISH) are eligible.
- •Metastatic (American Joint Committee on Cancer [AJCC] Stage IV) RCC
- •No prior systemic therapy for mRCC (patients with relapse >1 year after adjuvant treatment discontinuation are eligible)
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2
- •Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- •Frozen tumor samples or fresh tumor samples immediately stored in "RNA later" medium (primary tumor and/or metastasis biopsies) must be available and received by the central laboratory (Cordelier Research Center) to determine molecular groups. (Note: fine needle aspiration [FNA] and bone metastases samples are not acceptable for submission).
- •Formalin-fixed, paraffin-embedded (FFPE) tumor tissue available for biomarker (gene expression and immunohistochemistry (IHC)) analysis
- •Molecular group has to be determined prior to randomization.
排除标准
- •Any untreated CNS metastases. Patients with CNS metastases will be eligible if they are: asymptomatic, without significant edema, not on corticosteroids, not eligible for radiation therapy/surgery or have already received radiation therapy.
- •History of cerebrovascular accident including transient ischemic attack within the past 12 months.
- •History of DVT unless adequately treated with low molecular weight heparin
- •History of pulmonary embolism within the past 6m unless stable, asymptomatic, and treated with low molecular weight heparin for at least 6 weeks
- •Known history of COPD
- •Known history of uveitis or complaint of double vision
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months.
- •Serious, non-healing wound or ulcer
- •Evidence of active bleeding or bleeding susceptibility; or medically significant hemorrhage within prior 30 days.
- •Any requirement for anti-coagulation, except for low molecular weight heparin
- •Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
- •Prior systemic treatment with VEGF or VEGF receptor-targeted therapy (including, but not limited to, sunitinib, pazopanib, axitinib, tivozanib, and bevacizumab) except in an adjuvant setting with a free interval of more than 1 year.
- •Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- •Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection.
- •Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the Investigator’s opinion, would increase the risk associated with study participation or study drug administration, or interfere with the interpretation of safety results
- •Known history of hyperesthesia, hypoesthesia, paresthesia, dysesthesia, peripheral motor neuropathy, peripheral sensory, neuropathy, and polyneuropathy
- •Major surgery (e.g., nephrectomy) less than 35 days prior to the first dose of study drug
- •Focal radiation therapy less than 14 days prior to the first dose of study drug.
- •Receiving concomitant CYP3A4 inducers or strong CYP3A4 inhibitors
- •Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of TKI (e.g., malabsorptive disorder, ulcerative disease, uncontrolled nausea, vomiting, diarrhea, or small bowel resection).
- •Any of the following laboratory test findings: a) WBC <2,000/mm3 b) Hemoglobin ≤9.0 g/dL c) Neutrophils <1,500/mm3 d) Platelets <100,000/mm3 e) AST or ALT >3 x ULN (>5 x ULN if liver metastases are present) f) Lipase and amylase > 1.5 ULN g) Total Bilirubin >1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin <3.0 mg/dL) h) Serum creatinine >1.5 x ULN or creatinine clearance <40 mL/min (measured or calculated by Cockroft-Gault formula) i) Proteinuria: patients with ≥2+ protein on urine dipstick at baseline must undergo a 24-hour urine collection for protein then if > 1.0 g of protein patient will not be included.
- •Prior treatment with an anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- •Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (>10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type 1 diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll.
- •Any condition requiring systemic treatment with corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of SD. Inhaled steroids and adrenal replacement steroid doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- •Uncontrolled adrenal insufficiency
- •Ongoing symptomatic cardiac dysrhythmias, uncontrolled atrial fibrillation, or prolongation of the Fridericia corrected QT (QTcF) interval defined as >450 msec for males and >470 msec for females, where QTcF = QT / 3√RR.
- •Poorly controlled hypertension (defined as SBP of >150 mmHg or DBP of >90 mmHg), despite antihypertensive therapy
- •History of any of the following CV conditions within 12m of enrollment: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure, as defined by the NYHA.
结局指标
主要结局
Investigator-assessed ORR is defined as the proportion of randomized subjects who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) using RECIST 1.1 criteria based on Investigator assessments.
Investigator-assessed ORR is defined as the proportion of randomized subjects who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) using RECIST 1.1 criteria based on Investigator assessments.
次要结局
- Progression-free Survival The primary definition of PFS is specified as the time between randomization to the first date of documented progression, based on Investigator radiological assessments (as per RECIST 1.1 criteria), or death due to any cause, whichever occurs first. Subjects who die without a reported progression will be considered to have progressed on the date of their death.
- Overall Survival OS is defined as the time from randomization to the date of death from any cause. For subjects that are alive, their survival time will be censored at the date of last contact (“last known alive date”).
- Objective response rate at 22 weeks ORR at 22 weeks as defined as percentage of patients with an objective response (decrease of SLD by at least 30%) at second CT or MRI after treatment initiation.
- Duration of treatment Duration of treatment (DOT) is defined as the time between treatment initiation and discontinuation for any reason or End of study.
- Duration of response Duration of response (DOR) is defined as the time between response to treatment and discontinuation for any reason or End of study.
- AE Incidence Rate The AE incident rate is defined as the proportion of subjects with any-grade AEs among subjects in each treatment arm. Events reported from the first dose, up to and including 100 days following the last dose of study treatment will be included in calculating this incidence rate
研究者
Professor
Scientific
ARTIC
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