Phase I/II Study of Seleno-L Methionine (SLM) in Sequential Combination With Fixed Doses and Schedules of Axitinib and Pembrolizumab (SAP) in Locally Advanced and Metastatic Clear Cell Renal Cell Carcinoma (ccRCC)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Phase I - Dose limiting toxicities using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0
研究概览
简要总结
The purpose of this research study is to test the safety and effectiveness of Seleno-L Methionine (SLM) when combined with the standard dose and schedule of Axitinib and Pembrolizumab in patients who have locally advanced or metastatic clear cell renal cell carcinoma (ccRCC).
详细描述
The proposed study is a single arm, open-label Phase I/II trial of Seleno-L Methionine (SLM) in sequential combination with the standard dose and schedule of Axitinib and Pembrolizumab in previously untreated patients with advanced ccRCC. The hypothesis is that adding SLM to the Pembrolizumab and Axitinib combination will improve efficacy without added toxicity.
This is a two-part study:
- Escalation Part 1: The study will begin with a dose-escalation study to find the maximum tolerated dose (MTD) of study drug, SLM.
- Expansion Part 2: Once the appropriate dose of SLM is determined, the second part of the study will begin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be eligible to participate in this study, an individual must meet all the following criteria:
- •Written and voluntary informed consent.
- •Histologically and radiologically confirmed locally advanced or metastatic ccRCC. Locally advanced is defined as non resectable in the opinion of the treating providers. Participants must be treatment naïve in metastatic setting. Prior immunotherapy treatment in adjuvant setting is allowed.
- •> 18 years of age
- •At least one Response Evaluation Criteria in Solid Tumors (RECIST 1.1)-defined target lesion that has not been irradiated
- •Eastern Cooperative Oncology Group performance status of 0 (fully active, able to carry on all pre-disease performance without restriction) or 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, such as light housework or office work).
- •Renal function (creatinine level within normal institutional limit, or creatinine clearance >15 mL/min/1.73 m2 for patients with creatinine levels above institutional normal, calculated using the Cockcroft-Gault formula).
- •Liver function (AST/ALT <3.0 X institutional upper limit of normal OR < 5 x institutional upper limit of normal in cases of liver metastases; Total bilirubin ≤ 1.5 times ULN.)
- •Adequate hematological lab values including
- •Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L
- •Platelets ≥ 100 x 109/L
- •Hemoglobin ≥ 7.0 g/dL
- •Has adequately controlled BP with or without antihypertensive medications, defined as BP ≤150/90 mm Hg with no change in antihypertensive medications within 1 week before randomization/allocation.
- •Female subjects of childbearing potential and non-sterilized male subjects who intend to be sexually active during the study must agree to use a highly effective method of contraception from the time of screening, throughout the total duration of the drug treatment, and during the 6 month post-drug washout period. See section 5.6 for full details.
排除标准
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •Patients with a prior or concurrent malignancy whose natural history or treatment may have the potential to interfere with the safety or efficacy assessment of the investigational regimen.
- •Untreated metastases in the central nervous system.
- •Pregnant or breastfeeding.
- •Present use or anticipated need for cytochrome P450 (CYP) 3A4-inhibiting, CYP3A4-inducing drugs (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole, rifampin, phenytoin, carbamazepine, rifabutin, rifapentine, phenobarbital, and St. John's wort, bosentan, efavirenz, etravirine, modafinil, and nafcillin).
- •Myocardial infarction, uncontrolled angina, congestive heart failure, or cerebrovascular accident within previous 6 months. Participants with history of deep vein thrombosis or pulmonary embolism, at provider discretion.
- •Major surgery within 4 weeks of starting study treatment.
- •Patients with HIV infection with CD4+ T-cell (CD4+) counts < 350 cells/uL
- •Patients with HIV infection and a history of AIDS-defining opportunistic infections
- •No exclusions will be made based on sex, race, or ethnic background.
研究组 & 干预措施
Seleno-L Methionine (SLM) in Combination with Axitinib and Pembrolizumab
SLM only will be taken by mouth during a two-week run in period. Then patients will receive SLM and Axitinib drugs by mouth, and Pembrolizumab intravenously (IV), at the start of each 21 day cycle.
干预措施: Selenomethionine (SLM) (Drug)
Seleno-L Methionine (SLM) in Combination with Axitinib and Pembrolizumab
SLM only will be taken by mouth during a two-week run in period. Then patients will receive SLM and Axitinib drugs by mouth, and Pembrolizumab intravenously (IV), at the start of each 21 day cycle.
干预措施: Axitinib (Drug)
Seleno-L Methionine (SLM) in Combination with Axitinib and Pembrolizumab
SLM only will be taken by mouth during a two-week run in period. Then patients will receive SLM and Axitinib drugs by mouth, and Pembrolizumab intravenously (IV), at the start of each 21 day cycle.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Phase I - Dose limiting toxicities using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0
时间窗: From the initiation of treatment through three years
To examine the toxicity related to the therapy by measuring the number of treatment related adverse events in patients
Phase II - Objective Response Rate (ORR)
时间窗: From the initiation of treatment through three years
ORR will be defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1
次要结局
- Progression-free survival (PFS)(From the initiation of treatment through three years)
- Overall survival (OS)(From the initiation of treatment through three years)
研究者
Mohammed Milhem
Clinical Assistant Professor
University of Iowa