Combination Nivolumab and Ipilimumab With and Without Camu Camu in First Line Treatment of Metastatic Renal Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 31
- 试验地点
- 2
- 主要终点
- Abundance of ruminococcus in the stool
研究概览
简要总结
This phase I trial tests the safety, side effects, and best dose of camu camu when used in combination with nivolumab and ipilimumab in treating patients with kidney cancer that has spread to other places in the body. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). 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. Camu camu is a prebiotic that may have a beneficial effect on the immune system. Giving camu camu in combination with nivolumab and ipilimumab may kill more tumor cells than nivolumab and ipilimumab alone in patients with metastatic kidney cancer.
详细描述
PRIMARY OBJECTIVE:
I. To determine the effect of camu camu in combination with nivolumab/ipilimumab on Ruminococcus abundance in stool samples of patients with metastatic renal cell carcinoma (mRCC).
SECONDARY OBJECTIVES:
I. To evaluate the effect of camu camu on the clinical efficacy of the nivolumab/ipilimumab combination.
II. To determine the effect of camu camu on systemic immunodulation of the nivolumab/ipilimumab combination in patients with mRCC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Be willing and able to provide informed consent for the trial
- •Histological confirmation of renal cell carcinoma (RCC) with a clear-cell or sarcomatoid component
- •Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer [AJCC] 8 stage IV) RCC
- •Intermediate or poor risk disease by International Metastatic Renal Cell Carcinoma Database Consortium Criteria (IMDC) classification
- •No prior systemic therapy for RCC with the following exception:
- •One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such therapy did not include an agent that targets PD-1 or PD-L1 and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status < 2
- •Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- •Males and females, ages >= 18
- •Any ethnicity or race
- •Adequate renal function defined as calculated creatinine clearance >= 30 milliliters per minute (mL/min) per the Cockcroft and Gault formula or Serum creatinine < 1.5 x upper limit of normal (ULN)
- •Adequate liver function defined by aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x ULN (< 5 x ULN if liver metastases are present), and total bilirubin < 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin up to 3.0 mg/dL)
- •White blood cells (WBC) > 2,000/mm^3
- •Neutrophils > 1,500/mm^3
- •Platelets > 100,000/mm^3
排除标准
- •Presence of untreated brain metastases. Patients with treated brain metastases must be stable for 4 weeks after completion of treatment and have documented stability on pre-study imaging. Patients must have no clinical symptoms from brain metastases and have no requirement for systemic corticosteroids amounting to > 10 mg/day of prednisone or its equivalent for at least 2 weeks prior to first dose of study drug. Patients with known leptomeningeal metastases are excluded, even if treated
- •Favorable risk disease by IMDC classification
- •Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-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 I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
- •Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring treatment with systemic steroids
- •Baseline pulse oximetry less than 92% "on room air"
- •Current use, or intent to use probiotics, prebiotics, yogurt, bacterial fortified foods and other natural supplements =< 2 week prior to treatment initiation and during the period of treatment
- •Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
- •Uncontrolled adrenal insufficiency
- •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
- •Not recovered to =< Grade 1 toxicities related to any prior therapy before administration of study drug
- •Women who are pregnant or breastfeeding
- •History of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry
- •WBC < 2,000/mm^3
- •Neutrophils < 1,500/mm^3
- •Platelets < 100,000/mm^3
- •AST or ALT > 3 x ULN (> 5 x ULN if liver metastases are present)
- •Total bilirubin > 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin 3.0 mg/dL)
- •Calculated creatinine clearance <30 millimeters per minute (mL/min) per the Cockcroft and Gault formula or serum creatinine > 1.5 x upper limit of normal (ULN)
研究组 & 干预措施
Arm 1 (nivolumab and ipilimumab)
Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.
干预措施: Computed Tomography (Procedure)
Arm 1 (nivolumab and ipilimumab)
Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm 1 (nivolumab and ipilimumab)
Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.
干预措施: Biospecimen Collection (Procedure)
Arm 1 (nivolumab and ipilimumab)
Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.
干预措施: Ipilimumab (Biological)
Arm 1 (nivolumab and ipilimumab)
Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.
干预措施: Nivolumab (Biological)
Arm 2 (nivolumab, ipilimumab, camu camu)
Patients receive nivolumab IV over 30 minutes on day, ipilimumab IV over 30 minutes on day 1, and camu camu PO QD continuously with each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1, and camu camu PO QD of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.
干预措施: Nivolumab (Biological)
Arm 1 (nivolumab and ipilimumab)
Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.
干预措施: Bone Scan (Procedure)
Arm 2 (nivolumab, ipilimumab, camu camu)
Patients receive nivolumab IV over 30 minutes on day, ipilimumab IV over 30 minutes on day 1, and camu camu PO QD continuously with each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1, and camu camu PO QD of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.
干预措施: Biospecimen Collection (Procedure)
Arm 2 (nivolumab, ipilimumab, camu camu)
Patients receive nivolumab IV over 30 minutes on day, ipilimumab IV over 30 minutes on day 1, and camu camu PO QD continuously with each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1, and camu camu PO QD of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.
干预措施: Bone Scan (Procedure)
Arm 2 (nivolumab, ipilimumab, camu camu)
Patients receive nivolumab IV over 30 minutes on day, ipilimumab IV over 30 minutes on day 1, and camu camu PO QD continuously with each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1, and camu camu PO QD of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.
干预措施: Computed Tomography (Procedure)
Arm 2 (nivolumab, ipilimumab, camu camu)
Patients receive nivolumab IV over 30 minutes on day, ipilimumab IV over 30 minutes on day 1, and camu camu PO QD continuously with each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1, and camu camu PO QD of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm 2 (nivolumab, ipilimumab, camu camu)
Patients receive nivolumab IV over 30 minutes on day, ipilimumab IV over 30 minutes on day 1, and camu camu PO QD continuously with each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1, and camu camu PO QD of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.
干预措施: Myrciaria dubia Prebiotic Supplement (Drug)
Arm 2 (nivolumab, ipilimumab, camu camu)
Patients receive nivolumab IV over 30 minutes on day, ipilimumab IV over 30 minutes on day 1, and camu camu PO QD continuously with each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1, and camu camu PO QD of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.
干预措施: Ipilimumab (Biological)
结局指标
主要结局
Abundance of ruminococcus in the stool
时间窗: From baseline to week 12 of therapy
Using a two-group t-test with a one-sided type I error of 0.05.
次要结局
- Best overall response(Every 12 weeks for up to 3 years)
- Progression-free survival (PFS)(Time from enrollment to progression date or date of death, whichever occurs first (Each cycle is 4 weeks))
- Incidence of adverse events(Up to 30 days post-last dose of protocol therapy)