A Phase II Trial of Sitravatinib Plus Nivolumab in Patients With Metastatic Clear Cell Renal Cell Carcinoma Who Progressed on Prior Treatment Acronym: SNAPI (Sitravatinib and Nivolumab After Prior Immunotherapy)
概览
- 阶段
- 2 期
- 干预措施
- Nivolumab
- 疾病 / 适应症
- Advanced Clear Cell Renal Cell Carcinoma
- 发起方
- M.D. Anderson Cancer Center
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Disease control rate
- 状态
- 终止
- 最后更新
- 上个月
概览
简要总结
This phase II trial investigates the effect of sitravatinib and nivolumab in treating patients with clear cell renal cell cancer that has spread to other places in the body (metastatic/advanced). Sitravatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving sitravatinib and nivolumab may kill more tumor cells.
详细描述
PRIMARY OBJECTIVE: I. To determine the objective response rate (ORR) and disease control rate (DCR) at 24 weeks of sitravatinib 100 milligrams (mg) by mouth (PO) daily plus nivolumab 480 mg intravenously (IV) every 4 weeks in patients with metastatic renal cell carcinoma (mRCC) who progress on prior PD-1 or PD-L1 immune checkpoint inhibitors (CPIs), cabozantinib, or lenvatinib, as defined by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). SECONDARY OBJECTIVES: I. To estimate the overall survival (OS), progression-free survival (PFS), duration of response (DOR), and 1-year OS of sitravatinib plus nivolumab in the same population. II. To determine the safety, tolerability, and impact on health-related quality of life of sitravatinib plus nivolumab in patients with mRCC who progress on PD-1/PD-L1 CPIs, cabozantinib, or lenvatinib as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. EXPLORATORY OBJECTIVE: I. To assess how the immune landscape, transcriptome, and genome change after contemporary first-line treatment via tumor tissue biopsy obtained at time of enrollment, 4 weeks after treatment with sitravatinib plus nivolumab, and at time of progression, as well as blood sample collection. OUTLINE: Patients receive sitravatinib PO once daily (QD) and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.
研究者
入排标准
入选标准
- •Patients with histologically or cytologically confirmed metastatic/advanced clear cell RCC, or RCC with a clear cell component, who have received 1 or 2 prior lines of treatment in the advanced or metastatic setting, and the most recent treatment must include a PD-1 or PD-L1 CPI, cabozantinib, or lenvatinib. Examples of acceptable prior regimens include: nivolumab plus ipilimumab (cohort A), pembrolizumab plus axitinib, avelumab plus axitinib, or VEGF-targeted monotherapy followed by nivolumab monotherapy (cohort B), or cabozantinib or lenvatinib with or without everolimus, received alone sequentially before PD-1/PD-L1 inhibitors, or in combination with CPIs (cohort C)
- •There must be evidence of progression on or after treatment (at any point after completing prior therapy) with a PD-1/PD-L1-containing regimen as the last treatment received within 6 months of enrollment
- •Patients must have at least one measurable site of disease, defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures \>= 15 mm with conventional techniques or \>= 10 mm with more sensitive techniques such as magnetic resonance imaging (MRI) or spiral computed tomography (CT) scan. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
- •Karnofsky performance status \>= 70
- •Age \>= 18 years
- •Hemoglobin \>= 9 g/dl (treatment allowed)
- •May receive transfusion
- •Absolute neutrophil count \>= 1,000/uL
- •Platelets \>= 75,000/uL
- •Total bilirubin =\< 1.5 mg/dL
排除标准
- •Patients must not have any other malignancies within the past 2 years except for in situ carcinoma of any site, adequately treated (without recurrence post-resection or post- radiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of the skin, or active non-threatening second malignancy that would not, in the investigator's opinion, potentially interfere with the patient's ability to participate and/or complete this trial. Examples include but not limited to: urothelial cancer grade Ta or T1, adenocarcinoma of the prostate treated by active surveillance
- •Patients currently receiving anticancer therapies or who have received anticancer therapies within 2 weeks (14 days) from enrollment into this study (including chemotherapy and targeted therapy) are excluded. Also, patients who have completed palliative radiation therapy more than 14 days prior to the first dose of sitravatinib are eligible
- •Patients who had a major surgery or significant traumatic injury (injury requiring \> 28 days to heal) within 28 days of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia), or patients that are expected to require major surgery during the course of the study
- •Patients with a prior history of grade 3 or worse immune-related adverse events attributed to CPIs (PD-1, PD-L1, or CTLA-4), except endocrine adverse events with appropriate hormone replacement or asymptomatic amylase/lipase elevations
- •Active or prior documented autoimmune disease, as follows:
- •Inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
- •Interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
- •Other medically important autoimmune disease within 2 years before first dose of study treatment. Note: Patients with type 1 diabetes, vitiligo, Graves' disease requiring only hormone replacement, residual hypothyroidism requiring only hormone replacement, or psoriasis or Sjogren's syndrome not requiring systemic treatment are permitted
- •Immunocompromising conditions, as follows:
- •Known acute or chronic human immunodeficiency virus (HIV) infection
研究组 & 干预措施
Treatment (sitravatinib, nivolumab)
Patients receive sitravatinib PO QD and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Nivolumab
Treatment (sitravatinib, nivolumab)
Patients receive sitravatinib PO QD and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment
Treatment (sitravatinib, nivolumab)
Patients receive sitravatinib PO QD and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration
Treatment (sitravatinib, nivolumab)
Patients receive sitravatinib PO QD and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Sitravatinib
结局指标
主要结局
Disease control rate
时间窗: At 24 weeks
Will be defined by RECIST 1.1.
Objective response rate
时间窗: At 24 weeks
Will be defined as complete response + partial response. Will be defined by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
次要结局
- Overall survival(At 1 year)
- Incidence of adverse events(Up to 6 years)
- Progression free survival(At 1 year)
- Health-related quality-of-life (QOL)(Up to 24 weeks)
- Duration of response(At 1 year)