A Phase II Trial Of Lovastatin And Pembrolizumab In Patients With RM HNSCC (LAPP)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 28
- 试验地点
- 2
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
This phase II trial tests how well lovastatin and pembrolizumab work in treating patients with head and neck cancer that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Lovastatin is a drug used to lower the amount of cholesterol in the blood and may also cause tumor cell death. In addition, studies have shown that lovastatin may make the tumor cells more sensitive to immunotherapy. 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. Giving lovastatin and pembrolizumab may kill more tumor cells in patients with recurrent or metastatic head and neck cancer.
详细描述
PRIMARY OBJECTIVE:
I. To evaluate anti-tumor activity of the combination of pembrolizumab and lovastatin by assessing the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
SECONDARY OBJECTIVE:
I. To evaluate the anti-tumor activity of the combination of by assessing progression-free survival (PFS) and overall survival (OS).
TERTIARY/EXPLORATORY OBJECTIVES:
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients, male or female, aged ≥ 18, able to provide informed consent
- •Subjects with pathologically proven, recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) involving the oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, or paranasal sinuses; patients with unknown primary HNSCC involving the cervical lymph nodes can be included if human papillomavirus (HPV)-positive
- •PD-L1 combined positive score (CPS) ≥ 1 (i.e., must be a candidate for treatment with pembrolizumab alone)
- •Patients must not be under consideration for salvage surgery
- •Measurable disease by RECIST 1.1 criteria
- •Life expectancy of more than 3 months, as determined by the investigator
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Recovery to baseline or ≤ grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v.)5.0 from toxicities related to any prior treatments, unless adverse events are clinically non-significant and/or stable on supportive therapy
- •For men or women of reproductive potential: use of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 8 weeks after the end of lovastatin/pembrolizumab administration
- •Absolute neutrophil count (ANC) ≥ 1000/mm^3 without colony stimulating factor support
- •Platelets ≥ 100,000/mm^3
- •Hemoglobin ≥ 9 g/dL
- •Bilirubin ≤ 1.5 x the upper limit of normal (ULN). For subjects with known Gilbert's disease, bilirubin ≤ 3.0 mg/dL
- •Serum albumin ≥ 2.8 g/dl
- •Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.0 x ULN
- •Serum phosphorus, calcium, magnesium and potassium ≥ lower limit of normal (LLN)
排除标准
- •Patients already taking a statin drug
- •Liver dysfunction precluding the use of statins
- •Radiation to the head and neck or other sites within 4 weeks prior to enrollment
- •Cytotoxic chemotherapy or any form of investigational therapy within 4 weeks prior to study treatment
- •Prior treatment with immune checkpoint blocking therapy
- •Current use of drugs that interact with lovastatin (cimetidine, spironolactone, ketoconazole, and others)
- •Pregnancy, lactation, or plan to become pregnant
- •Inability to swallow lovastatin tablets
- •Known allergy or prior adverse reaction to lovastatin, other statin drugs, or pembrolizumab
研究组 & 干预措施
Treatment (lovastatin, pembrolizumab)
Patients receive lovastatin PO QD and pembrolizumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, and CT, MRI or PET/CT throughout the study.
干预措施: Computed Tomography (Procedure)
Treatment (lovastatin, pembrolizumab)
Patients receive lovastatin PO QD and pembrolizumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, and CT, MRI or PET/CT throughout the study.
干预措施: Lovastatin (Drug)
Treatment (lovastatin, pembrolizumab)
Patients receive lovastatin PO QD and pembrolizumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, and CT, MRI or PET/CT throughout the study.
干预措施: Biospecimen Collection (Procedure)
Treatment (lovastatin, pembrolizumab)
Patients receive lovastatin PO QD and pembrolizumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, and CT, MRI or PET/CT throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Treatment (lovastatin, pembrolizumab)
Patients receive lovastatin PO QD and pembrolizumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, and CT, MRI or PET/CT throughout the study.
干预措施: Pembrolizumab (Biological)
Treatment (lovastatin, pembrolizumab)
Patients receive lovastatin PO QD and pembrolizumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, and CT, MRI or PET/CT throughout the study.
干预措施: Positron Emission Tomography (Procedure)
结局指标
主要结局
Objective response rate (ORR)
时间窗: Up to 1 year
ORR will be defined as the proportion of subjects with partial response or complete response. ORR will be evaluated using Response Evaluation Criteria in Solid Tumors version (RECIST) (v)1.1 response criteria. ORR will be calculated with 95% confidence interval by binomial distribution.
次要结局
- Progression free survival (PFS)(From date of treatment start to the date of objectively documented progression or death due to any cause, whichever status is recorded first, assessed up to 1 year)
- Overall survival (OS)(Up to 1 year)
- Incidence of adverse events (AEs) and serious adverse events (SAEs)(Up to 30 days after last dose of study treatment)
研究者
Nicole Schmitt
Principal Investigator
Emory University