A Phase II Study of Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This study will examine the combination of pembrolizumab and tadalafil for safety and efficacy in advanced head and neck cancer.
详细描述
Immune competent animal models of HNSCC demonstrate that combination PDE-5 inhibitor (tadalafil) and PD-1 inhibitor therapy is more effective than either therapy alone based on the concept of targeting multiple immune repressive abnormalities simultaneously (PD-1 checkpoint and myeloid suppressive pathways).
This trial will test the hypothesis that combination PD-1 inhibition and PDE-5 inhibition can be safely co-administered, and secondarily test the hypothesis that the combination of both therapies will be more effective than PD-1 inhibition alone in recurrent/metastatic HNSCC.
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
- •Selected Inclusion Criteria:
- •Patients (at least 18 years of age) must have recurrent or metastatic squamous cell carcinoma of the head and neck.
- •Presence of measurable disease.
- •Life expectancy of greater than 12 weeks
- •Patients must have normal organ and marrow function
排除标准
- •Prior therapy with an PD-1 or PD-L1 inhibitor in the recurrent or metastatic setting
- •Uncontrolled central nervous system metastases (stable metastases permitted)
- •Active autoimmune disease
- •Chemotherapy ≤28 days prior to first administration of study treatment and/or monoclonal antibody ≤8 weeks prior to first administration of study treatment.
- •Prior daily use of tadalafil or other long-acting PDE5 inhibitors for one month or greater within 3 months of trial enrollment
- •Current use of all other long-acting PDE5 inhibitors.
- •Known severe hypersensitivity to tadalafil or any of the excipients of this product
- •Current treatment with nitrates
- •Current systemic treatment with a potent cytochrome P450 3A4 (CYP3A4) inhibitor such as ketoconazole or ritonavir.
- •Current treatment with guanylate cyclase (GC) stimulators such as riociguat.
- •History of hypotension and/or blindness and/or sensorineural hearing loss during prior treatment with tadalafil or other PDE-5 inhibitors
- •History of known hereditary degenerative retinal disorders, including retinitis pigmentosa
- •Prior history of non-arteritic anterior ischemic optic neuropathy
- •Pregnant or breastfeeding; a negative pregnancy test is required within 14 days of randomization for all women of childbearing potential.
- •History of stroke within prior 6 months.
- •History of acute myocardial infarction within prior 3 months, uncontrolled angina, uncontrolled arrhythmia, or uncontrolled congestive heart failure
- •Left ventricular outflow obstructions, such as aortic stenosis and idiopathic hypertrophic subaortic stenosis
- •Angina requiring treatment with long-acting nitrates
- •Angina requiring treatment with short-acting nitrates within 90 days of planned tadalafil administration
- •Unstable angina within 90 days of visit 1 (Braunwald 1989)
- •Positive cardiac stress test without documented evidence of subsequent, effective cardiac intervention
- •History of any of the following coronary conditions within 90 days of planned tadalafil administration:
- •Myocardial Infarction
- •Coronary artery bypass graft surgery
- •Percutaneous coronary intervention (for example, angioplasty or stent placement)
- •Any evidence of heart disease (NYHA ≥ Class II as defined in Protocol Attachment LVHG.3) within 6 months of planned tadalafil administration
- •Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration of >10 mg/day of prednisone or equivalent)
- •Prior organ transplantation
- •Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).
研究组 & 干预措施
Tadalafil and Pembrolizumab
Tadalafil for up to 12 months and pembrolizumab for up to 24 months.
干预措施: Pembrolizumab (Drug)
Tadalafil and Pembrolizumab
Tadalafil for up to 12 months and pembrolizumab for up to 24 months.
干预措施: Tadalafil (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: 12 months
Overall survival at 12 months post-enrollment
Rate of Dose Limiting Toxicity (DLT)
时间窗: 2 years
Rate of dose limiting toxicity at least possibly attributable to study treatment
次要结局
- Response Measured by RECIST 1.1(12 months)
- Progression Free Survival(2 years)
- Adverse Event Rates(2 years)
研究者
Joseph Califano
Professor of Medicine
University of California, San Diego