Impact of Microbiome Modulation With CBM588 in Combination With Pembrolizumab for Adjuvant Therapy of High-Risk, Resected Renal Cell Carcinoma (RCC)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 62
- 试验地点
- 4
- 主要终点
- Change in interleukin (IL)-12 levels
研究概览
简要总结
This phase II trial compares the effect of adding a Live Biotherapeutic Product called CBM588 to pembrolizumab versus pembrolizumab alone in preventing return of disease (recurrence) after surgery for patients with renal cell cancer. Pembrolizumab is an immune checkpoint inhibitor. Immunotherapy with monoclonal antibodies such as pembrolizumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pembrolizumab is approved for the treatment of renal cell cancer after surgery. Research has shown that changes to the composition of the healthy bacteria in the body (the microbiome), may improve a patient's response to treatment with immunotherapy. CBM588, a Live Biotherapeutic Product (LBP) containing a bacteria called Clostridium butyricum, has been shown to improve outcomes in patients treated with immunotherapy for other types of cancer. Adding CBM588 to treatment with pembrolizumab after surgery may cause changes in the microbiome that improve patient response to treatment and reduce disease recurrence, compared to pembrolizumab alone.
详细描述
PRIMARY OBJECTIVE:
I. To determine if the Clostridium butyricum CBM588 strain (CBM588) increases interleukin (IL)-12 production in patients with high-risk, resected renal cell carcinoma (RCC) receiving pembrolizumab.
SECONDARY OBJECTIVES:
I. To determine if CBM588 improves recurrence-free survival (RFS) in patients with high-risk, resected renal cell carcinoma (RCC) receiving pembrolizumab.
II. To determine if CBM588 improves overall survival (OS) in patients with high-risk, resected renal cell carcinoma (RCC) receiving pembrolizumab.
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
- •Pathologic stage of pT2, G4 or sarcomatoid, N0M0; pT3, any grade, N0M0; pT4, any grade, N0M0; pTany, any grade, N+M0; or M1 no evidence of disease (NED) after resection
- •No prior systemic immunotherapy for RCC
- •Eastern Cooperative Oncology Group (ECOG) performance status < 2
- •Males and females, ages ≥ 18
- •Any ethnicity or race
- •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)
- •Aspartate aminotransferase (AST) or alanine aminotransferase (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 up to 3.0 mg/dL)
- •Adequate bone marrow function defined by any of the following laboratory test findings: white blood cells (WBC) > 2,000/mm^3, neutrophils > 1,500/mm^3, platelets > 100,000/mm^3
- •Female subjects of child-bearing potential and female partners of male subjects must agree to use a highly effective method of contraception during treatment and for at least 5 months after the last dose
- •Highly effective methods of contraception include: tubal ligation, an approved hormonal contraceptive such as oral contraceptives, patches, implants, injections, rings or hormonally impregnated intrauterine device (IUD), or IUD
排除标准
- •Prior radiation or anti-PD1, anti-PDL1, or anti-CTLA-4 therapy for RCC
- •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 weeks 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
研究组 & 干预措施
Arm 1 (CBM588, pembrolizumab)
Patients receive CBM588 PO BID on days 1-21 or days 1-42 of each cycle and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm 1 (CBM588, pembrolizumab)
Patients receive CBM588 PO BID on days 1-21 or days 1-42 of each cycle and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT throughout the study.
干预措施: Clostridium butyricum CBM588 Strain (Drug)
Arm 2 (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT throughout the study.
干预措施: Pembrolizumab (Biological)
Arm 1 (CBM588, pembrolizumab)
Patients receive CBM588 PO BID on days 1-21 or days 1-42 of each cycle and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT throughout the study.
干预措施: Pembrolizumab (Biological)
Arm 1 (CBM588, pembrolizumab)
Patients receive CBM588 PO BID on days 1-21 or days 1-42 of each cycle and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT throughout the study.
干预措施: Computed Tomography (Procedure)
Arm 2 (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm 2 (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT throughout the study.
干预措施: Computed Tomography (Procedure)
结局指标
主要结局
Change in interleukin (IL)-12 levels
时间窗: Baseline to week 12
A two-sample t-test will be used to test the difference in the changes in IL-12 production for the two treatment arms. A Wilcoxon rank-sum test will be used if the changes are not normally distributed (p\< 0.05 by a Shapiro-Wilks test).
次要结局
- Recurrence-free survival (RFS)(From randomization to disease recurrence or death, assessed up to 1 year)
- Overall survival (OS)(From randomization to death from any cause, assessed up to 1 year)
- Shannon diversity index(Baseline to week 12)
- Proportion of circulating regulatory T cells (Tregs)(Baseline to week 12)
- Proportion of circulating myeloid derived suppressor cells (MDSCs)(Baseline to week 12)
- IL-6, IL-8 and other cytokines/chemokines(Baseline to week 12)
- Incidence of toxicities(Up to 30 days after last dose)