Targeting Inflammaging-Associated Cytokine Signaling to Improve Efficacy and Reduce Immune-Related Toxicities of Anti-PD-1/CTLA-4 Therapy
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Tolerated dose of the combination of anakinra and tocilizumab that can be used in conjunction with nivolumab and ipilimumab in patients 50 years or older
研究概览
简要总结
This phase I trial studies the side effects of adding anakinra and tocilizumab to standard treatment with nivolumab and ipilimumab and to see how well it works in treating melanoma patients who are 50 years of age or older. Anakinra and tocilizumab are used to decrease the body's immune response and lower side effects. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Researchers think that anakinra and tocilizumab may reduce the side effects experienced from standard treatment with nivolumab and ipilimumab while also preserving their anti-cancer effects. Adding anakinra and tocilizumab to standard treatment with nivolumab and ipilimumab may be safe, tolerable, and/or effective in treating melanoma patients who are 50 years of age or older.
详细描述
PRIMARY OBJECTIVES:
I. To establish the tolerated dose of the combination of anakinra and tocilizumab that can be used in conjunction with nivolumab and ipilimumab for further evaluation in patients 50 years of age or older at the start of treatment.
SECONDARY OBJECTIVES:
I. To evaluate the safety of the combination based on Common Terminology Criteria for Adverse Events (CTCAE) version (v) 6.0.
II. To evaluate the incidence of discontinuation of immune checkpoint inhibitor (ICI) therapy due to grade 3 or higher immune-related adverse events (irAEs).
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
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 50 years old
- •Patients with melanoma, who are going to be treated with ipilimumab 1mg/Kg and nivolumab 3mg/Kg as a standard of care (SOC)
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- •Platelets ≥ 50 000/µL
- •Hemoglobin ≥ 8.0 g/dL
- •Absolute neutrophil count (ANC) ≥ 1500/μL
- •Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) ≤ 3.0 X institutional ULN (up to 5 X institutional ULN if patient has liver metastases)
- •Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3.0 X institutional ULN (up to 5 X institutional ULN if patient has liver metastases)
- •Creatinine < 2.0 ULN
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- •Willingness to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol
排除标准
- •Patients must not be receiving other concomitant biologic therapy, targeted therapy, chemotherapy, other anti-cancer therapy or any other investigational agents while on this protocol
- •Immunosuppressive systemic corticosteroids equivalent to prednisone 10 mg or greater in the 14 days prior to the first cycle
- •Active autoimmune disease requiring systemic treatment in the past 2 years (i.e. use of disease modifying agents or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment
- •Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness / social situations that would limit compliance with study requirements
- •Positive pregnancy test, active pregnancy or nursing / breast-feeding, due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
- •History of solid organ or bone marrow transplantation
- •Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
研究组 & 干预措施
Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)
Patients receive anakinra SC QD on days 1-21 of each cycle, once every other day of each cycle, or once every 3 days of each cycle. Patients also receive tocilizumab IV, nivolumab IV, and ipilimumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and CT or PET/CT during screening and as clinically indicated as well as blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)
Patients receive anakinra SC QD on days 1-21 of each cycle, once every other day of each cycle, or once every 3 days of each cycle. Patients also receive tocilizumab IV, nivolumab IV, and ipilimumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and CT or PET/CT during screening and as clinically indicated as well as blood sample collection throughout the study.
干预措施: Computed Tomography (Procedure)
Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)
Patients receive anakinra SC QD on days 1-21 of each cycle, once every other day of each cycle, or once every 3 days of each cycle. Patients also receive tocilizumab IV, nivolumab IV, and ipilimumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and CT or PET/CT during screening and as clinically indicated as well as blood sample collection throughout the study.
干预措施: Electronic Health Record Review (Other)
Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)
Patients receive anakinra SC QD on days 1-21 of each cycle, once every other day of each cycle, or once every 3 days of each cycle. Patients also receive tocilizumab IV, nivolumab IV, and ipilimumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and CT or PET/CT during screening and as clinically indicated as well as blood sample collection throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)
Patients receive anakinra SC QD on days 1-21 of each cycle, once every other day of each cycle, or once every 3 days of each cycle. Patients also receive tocilizumab IV, nivolumab IV, and ipilimumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and CT or PET/CT during screening and as clinically indicated as well as blood sample collection throughout the study.
干预措施: Positron Emission Tomography (Procedure)
Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)
Patients receive anakinra SC QD on days 1-21 of each cycle, once every other day of each cycle, or once every 3 days of each cycle. Patients also receive tocilizumab IV, nivolumab IV, and ipilimumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and CT or PET/CT during screening and as clinically indicated as well as blood sample collection throughout the study.
干预措施: Anakinra (Biological)
Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)
Patients receive anakinra SC QD on days 1-21 of each cycle, once every other day of each cycle, or once every 3 days of each cycle. Patients also receive tocilizumab IV, nivolumab IV, and ipilimumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and CT or PET/CT during screening and as clinically indicated as well as blood sample collection throughout the study.
干预措施: Tocilizumab (Biological)
Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)
Patients receive anakinra SC QD on days 1-21 of each cycle, once every other day of each cycle, or once every 3 days of each cycle. Patients also receive tocilizumab IV, nivolumab IV, and ipilimumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and CT or PET/CT during screening and as clinically indicated as well as blood sample collection throughout the study.
干预措施: Ipilimumab (Biological)
Treatment (anakinra, tocilizumab, nivolumab, ipilimumab)
Patients receive anakinra SC QD on days 1-21 of each cycle, once every other day of each cycle, or once every 3 days of each cycle. Patients also receive tocilizumab IV, nivolumab IV, and ipilimumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and CT or PET/CT during screening and as clinically indicated as well as blood sample collection throughout the study.
干预措施: Nivolumab (Biological)
结局指标
主要结局
Tolerated dose of the combination of anakinra and tocilizumab that can be used in conjunction with nivolumab and ipilimumab in patients 50 years or older
时间窗: Up to 12 weeks
次要结局
- Incidence of discontinuation of immune checkpoint inhibitor therapy due to grade 3 or higher immune-related adverse events(Up to 12 weeks)
- Objective response rate(Up to 2 years)
- Overall survival(From first dose of treatment to death due to any cause, assessed up to 2 years)
- Progression free survival (PFS)(From start of treatment to time of progression or death whichever comes first, assessed up to 2 years)