Phase II Trial of Avelumab (Bavencio) With IL-15 in Subjects With Clear-Cell Renal Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Overall Response Rate (Complete Response + Partial Response)
研究概览
简要总结
Background:
-Clear-cell renal cell carcinoma (ccRCC) is a kind of kidney cancer. The drug avelumab may help direct the immune response to the tumors and can prolong the immune response. The drug Interleukin-15 (IL-15) stimulates certain kinds of white blood cells that have the potential to attack the cancer.
Objective:
-To test whether IL-15 and avelumab administered together are safe and effective at treating ccRCC.
Eligibility:
-People ages 18 and older with relapsed, metastatic biopsy proven clear cell renal cell carcinoma (ccRCC) that has not responded to standard treatments
Design:
Participants will be screened with:
- Medical history
- Physical exam
- Blood, urine, heart, and lung tests
- Computed tomography (CT) and positron emission tomography (PET) scans and possible MRI: Participants will lie in a machine that takes pictures of the body. For the CT scan, they may receive an oral contrast agent by mouth and normally receive IV contrast through a vein to improve the x-ray images.
- Tumor sample to confirm expression of avelumab target: If one is not available, participants will require a new biopsy that is generally obtained by a needle that is inserted into the tumor.
Participants will get the study drugs by vein for up to four 28-day cycles. The IL-15 will be given through a vein continuously for the first 5 days (120 hours) of each cycle. They avelumab will be given through a vein over about 1 hour on days 8 and 22 of each cycle. Participants will be hospitalized for their 1st week of IL-15 cycle and may be able to receive their subsequent IL-15 treatment as an outpatient depending on their side effects. Participants who receive the infusion as an outpatient will return to the hospital each day for a new bag of IL-15. Participants who cannot or do not want to be treated as an outpatient will be treated in the hospital during their 5-day IL-15 infusions.
- Participants will need a midline venous catheter which is longer than a standard venous catheter but is still inserted into a peripheral vein in their arm.
- Participants will have repeats of blood tests to monitor the blood counts and chemistry throughout the study.
- Participants will have follow-up visits 30 days after their last treatment, every 60 days for the first 6 months, every 90 days for 2 years, then every 6 months.
详细描述
Background:
- Clear-cell renal cell carcinoma (ccRCC) is among the 10 most frequent diagnostic cancers in the United States with more than an estimated 62,000 new cases in 2016. The prognosis for patients with metastatic disease is poor with survival rates of 8%.
- The immunologic effects of recombinant human Interleukin-15 (rhIL-15), a stimulatory cytokine that promotes the differentiation and activation of NK cells, monocytes and long term cluster of differentiation 8 (CD8)+ memory T-cells, has been assessed in several Phase 1 trials in cancer patients.
- Avelumab is an anti-programmed death ligand-1 (PD-L1) fully human immunoglobulin G1 (IgG1) antibody that inhibits programmed cell death protein 1 (PD1)/PD-L1 interactions while leaving the PD1/Programmed cell death 1 ligand 2 (PD-L2) pathway intact and enhances immune activation against tumor cells. It has received United States (U.S.) Food and Drug Administration (FDA) accelerated approval for the treatment of patients with metastatic Merkel cell carcinoma (MCC) and urothelial carcinoma.
- Unlike other approved anti-PD-L1/PD1 antibodies, avelumab induces lysis of tumor cells via antibody-dependent cell-mediated cytotoxicity (ADCC), indicating an additional mechanism of action. However, avelumab has not shown ADCC against normal immune cell subsets in humans.
- More than 50% of ccRCC is PD-L1+ with higher expression in unfavorable prognostic tumors. Since the anti-PD-L1 antibody avelumab has shown ADCC activity in vitro, agents that may enhance ADCC by increasing number and activity of Fc-binding effector cells -such as recombinant human Interleukin-15 (rhIL-15) - could improve efficacy of avelumab in this disease.
Objectives:
-Determine the efficacy of combined continuous intravenous infusion (CIV) rhIL-15 and avelumab treatment in patients with anti-PD-1/PD-L1 refractory metastatic clear cell renal carcinoma (ccRCC) by assessing the overall response rate
Eligibility:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm 1- Experimental Treatment: Safety Run-in
Interleukin 15 (IL-15) by continuous intravenous (CIV) infusion at escalating doses of 2 and 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 4 cycles) with avelumab by intravenous (IV) infusion at a dose of 800mg on Day 8 and 22 of each cycle
干预措施: rhIL-15 (Drug)
Arm 1- Experimental Treatment: Safety Run-in
Interleukin 15 (IL-15) by continuous intravenous (CIV) infusion at escalating doses of 2 and 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 4 cycles) with avelumab by intravenous (IV) infusion at a dose of 800mg on Day 8 and 22 of each cycle
干预措施: Avelumab (Biological)
Arm 2-Experimental Treatment: Dose Expansion
Interleukin 15 (IL-15) by continuous intravenous (CIV) infusion at 4 mcg/kg/day on days 1-5 of each 28- day cycle (max 4 cycles) with avelumab by intravenous (IV) infusion at a dose of 800mg on Day 8 and 22 of each cycle
干预措施: rhIL-15 (Drug)
Arm 2-Experimental Treatment: Dose Expansion
Interleukin 15 (IL-15) by continuous intravenous (CIV) infusion at 4 mcg/kg/day on days 1-5 of each 28- day cycle (max 4 cycles) with avelumab by intravenous (IV) infusion at a dose of 800mg on Day 8 and 22 of each cycle
干预措施: Avelumab (Biological)
结局指标
主要结局
Overall Response Rate (Complete Response + Partial Response)
时间窗: Following start of study medication while on treatment, approximately 2 months.
Response was assessed using the Immune Related Response Evaluation Criteria in Solid Tumors (irRECIST)v1.1. Immune related complete response (irCR) is at least two radiographic determinations of complete response (CR - e.g., disappearance of all target lesions) at least 4 weeks apart and before Immune related progressive disease (irPD - defined as at least two consecutive radiographic determinations of progressive disease ((PD - e.g., appearance of one or more new lesions) at least 4 weeks apart). at least 4 weeks apart). Immune related partial response (irPR) is at least two radiographic determinations of partial response (PR - e.g., 30% decrease of target lesions) or better at least 4 weeks apart and before irPD (and not qualifying for an irCR).
次要结局
- Overall Survival(time from the date of study enrollment until time of death from any cause, an average of 167 days)
- Duration of Response(Following start of study medication while on treatment, up to 1-2 months.)
- Number of Grade 3 Adverse Events Possibly, Probably or Definitely Related to Treatment of rhIL-15 + Avelumab(4 cycles (each cycle is 28 days), up to 112 days)
- Progression-free Survival(Monitoring frequency is every two cycles through completion of study then annually until progressive disease is noted, an average of 73 days.)
研究者
Kevin Conlon, MD
Principal Investigator
National Cancer Institute (NCI)