Phase I Study of 5-Azacitidine Plus PD-1/PD-L1 Inhibitor in Patients With PD-1/PD-L1 Refractory Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Incidence of dose-limiting toxicities and responses as defined by CTCAE v5.0
研究概览
简要总结
This is a Phase I study to determine the optimal biological dose (OBD) of 5-Azacitidine in combination with PD-1/PD-L1 inhibitors in patients with tumors refractory to PD-1/PD-L1 inhibitors, for which such treatments have been approved.
详细描述
This is a Phase I study to determine the optimal biological dose (OBD) of 5-Azacitidine in combination with PD-1/PD-L1 inhibitors in patients with tumors refractory to PD-1/PD-L1 inhibitors, for which such treatments have been approved.
This Phase I study will assess 6 doses of 5-Azacitidine (5, 10, 15, 25, 50 and 75 mg/m2) in combination with a PD1/PD-L1 inhibitor. The PD1/PD-L1 inhibitor will be given at standard of care dosing approved by the FDA for this indication.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written and voluntary informed consent.
- •At least 18 years of age or older.
- •Histologically and radiologically confirmed locally advanced or metastatic unresectable solid tumor malignancy for which PD-1 or PD-L1 therapy is already approved by the FDA. Locally advanced is defined as unresectable in the opinion of the treating physician. A repeat biopsy is required if previous biopsy tissue is unavailable.
- •At least one Response Evaluation Criteria in Solid Tumors (RECIST 1.1) - defined target lesion.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 (fully active, able to carry on all pre-disease performance without restriction), 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), or 2 (ambulatory and capable of self-care but unable to carry out any work activities, spending more than 50% of waking hours up and about).
- •Documented progression on PD1 or PD-L1 inhibitors.
- •Recovery from any acute toxicity associated with prior therapy to grade
- •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 metastasis; total bilirubin ≤ 1.5 times upper limit of normal).
- •Adequate hematological lab values including:
- •Absolute Neutrophil Count (ANC) ≥ 1.0 X 109/L
- •Platelets ≥ 100X109/L
- •Hemoglobin ≥ 7.0 g/dL
- •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 time of screening, throughout the whole duration of the drug treatment, and during the 6-month post-treatment washout period.
- •Patients may have previously received a hypomethylating agent, as long as it was not given in combination with ipilimumab.
- •Patients may have previously received ipilimumab but must have relapsed or progressed while on therapy.
- •Patients must have adequate archival tissue available for the purpose of downstream methylation status assessment, immunohistochemistry, RNA expression (10 slides at 5µM). If archival tissue is not available, a repeat biopsy is required.
排除标准
- •Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
- •Patients with active, untreated metastases in the central nervous system.
- •Patients who are pregnant or breastfeeding.
- •Patients who have an active infection.
- •Patients with significant hematologic, hepatic, and renal function impairment.
- •Patients who are being treated for any concurrent medical condition requiring the use of systemic steroids or history of long-term use of systemic steroids.
- •Patients who have a history of inflammatory bowel disease or a history of symptomatic autoimmune disease.
- •Patients who have had any major surgical procedure or significant traumatic injury within 28 days prior to study enrollment.
- •Patients who have received chemotherapy, immunosuppressive agents or any investigational drug within 28 days prior to starting the study drugs.
- •Patients who have any underlying medical condition which, in the treating physician's opinion, will make the administration of study drugs hazardous or obscure the interpretation of adverse events.
研究组 & 干预措施
5-Azacitidine Plus PD-1/PD-L1 inhibitor
This Phase I study will assess 6 doses of 5-Azacitidine (5, 10, 15, 25, 50 and 75 mg/m2) in combination with a PD1/PD-L1 inhibitor. The PD1/PD-L1 inhibitor will be given at standard of care dosing approved by the FDA for this indication. Inhibitors approved for study indications include Pembrolizumab, Nivolumab, and Cemiplimab.
干预措施: Pembrolizumab (Drug)
5-Azacitidine Plus PD-1/PD-L1 inhibitor
This Phase I study will assess 6 doses of 5-Azacitidine (5, 10, 15, 25, 50 and 75 mg/m2) in combination with a PD1/PD-L1 inhibitor. The PD1/PD-L1 inhibitor will be given at standard of care dosing approved by the FDA for this indication. Inhibitors approved for study indications include Pembrolizumab, Nivolumab, and Cemiplimab.
干预措施: 5 Azacytidine (Drug)
5-Azacitidine Plus PD-1/PD-L1 inhibitor
This Phase I study will assess 6 doses of 5-Azacitidine (5, 10, 15, 25, 50 and 75 mg/m2) in combination with a PD1/PD-L1 inhibitor. The PD1/PD-L1 inhibitor will be given at standard of care dosing approved by the FDA for this indication. Inhibitors approved for study indications include Pembrolizumab, Nivolumab, and Cemiplimab.
干预措施: Cemiplimab (Drug)
5-Azacitidine Plus PD-1/PD-L1 inhibitor
This Phase I study will assess 6 doses of 5-Azacitidine (5, 10, 15, 25, 50 and 75 mg/m2) in combination with a PD1/PD-L1 inhibitor. The PD1/PD-L1 inhibitor will be given at standard of care dosing approved by the FDA for this indication. Inhibitors approved for study indications include Pembrolizumab, Nivolumab, and Cemiplimab.
干预措施: Nivolumab (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities and responses as defined by CTCAE v5.0
时间窗: Treatment initiation through 30 days +/- 7 days post completion of therapy
Assess the safety and tolerability of 5-Azacitidine Plus PD-1/PD-L1 inhibitor
次要结局
- Proportion of participants with a complete response (CR)(Treatment initiation through five years)
- Proportion of participants with a partial response (PR)(Treatment initiation through five years)
- Overall Survival (OS)(Treatment initiation through five years)
- Progression Free Survival (PFS)(Treatment initiation through five years)
研究者
Mohammed Milhem
Clinical Professor
University of Iowa