Safety and Efficacy of Ruxolitinib in Patients With Head and Neck Squamous Cell Carcinoma and High Neutrophil-to-Lymphocyte Ratio Treated With Pembrolizumab - The Phase 2 InflammaSTOP Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 66
- 试验地点
- 10
- 主要终点
- 6-Month Progression-Free Survival Rate (R/M cohort only)
研究概览
简要总结
The goal of this Phase 2 clinical trial is to learn if adding ruxolitinib to pembrolizumab may improve treatment outcomes in patients with head and neck squamous cell carcinoma (HNSCC) who have increased levels of systemic inflammation before treatment, as measured by the neutrophil-to-lymphocyte ratio (NLR). The investigational drug will be used outside of its approved indication (off-label use) based on its known pharmacologic mechanism and prior clinical experience in patients with myeloproliferative neoplasms and graft-versus-host disease.
The main questions it aims to answer are:
Is treatment with ruxolitinib in combination with pembrolizumab safe and well tolerated? Can the addition of ruxolitinib improve treatment outcomes compared with historical data? How does ruxolitinib affect the immune system and inflammation when given together with pembrolizumab? How does the combination treatment affect patients' quality of life?
Participants will:
Receive treatment with pembrolizumab and intermittent ruxolitinib. Undergo blood tests to assess immune responses and inflammation. Attend study visits for safety assessments and treatment monitoring. Complete quality-of-life questionnaires, where applicable.
The results of this study will help researchers better understand how inflammation and the body's immune system affect treatment outcomes in people with head and neck cancer. The findings may also help improve the design of future studies investigating new treatment combinations for this disease.
详细描述
Head and neck squamous cell carcinoma (HNSCC) remains associated with poor outcomes in a substantial proportion of patients despite the introduction of immune checkpoint inhibitors. An elevated neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has been associated with reduced survival in patients receiving immune checkpoint inhibitor therapy and may identify a subgroup of patients at increased risk of poor treatment outcomes.
Janus kinase (JAK) inhibition represents a potential strategy to modulate cancer-associated systemic inflammation and the tumor immune microenvironment. Ruxolitinib, a JAK1/2 inhibitor, has demonstrated anti-inflammatory effects and may enhance the activity of immune checkpoint inhibition by reducing inflammatory signaling pathways that could contribute to treatment resistance.
This study uses a biomarker-driven treatment approach in patients with PD-L1-positive recurrent, metastatic, or locally advanced HNSCC who have evidence of increased systemic inflammation prior to treatment initiation. The study is designed to investigate the effects of combining pembrolizumab with intermittent ruxolitinib and to evaluate whether this approach can favorably influence systemic inflammation and immune responses while maintaining acceptable tolerability.
Patients with advanced HNSCC are frequently frail and may be unable to tolerate the toxicities associated with conventional chemotherapy-based treatment approaches. Consequently, there is a need for treatment strategies that are both effective and well tolerated in patients with reduced performance status. The present study therefore focuses on a population with an inflammatory high-risk phenotype and seeks to generate clinical and translational evidence to support future treatment development.
In addition to evaluating the clinical activity and tolerability of the combination regimen, the study will characterize treatment-associated changes in systemic inflammation and adaptive immune responses. The findings are intended to provide a better understanding of the relationship between inflammatory biomarkers, immune modulation, and clinical outcomes in HNSCC, and to inform the design of future randomized studies evaluating JAK inhibition in combination with immune checkpoint blockade.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Histologically confirmed diagnosis of R/M HNSCC without local treatment options planned for treatment with pembrolizumab monotherapy (R/M cohort) or locally advanced HNSCC planned for perioperative treatment with pembrolizumab (neoadjuvant cohort)
- •PD-L1 CPS≥1
- •ECOG-performance score 0-2
- •NLR >4 before start of pembrolizumab treatment
- •Signed and dated written informed consent
排除标准
- •Participation in another interventional study simultaneously and within the last 30 days prior to inclusion
- •Concurrent malignancies other than disease under study within 5 years prior to inclusion, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
- •Active, known, or suspected autoimmune disease requiring systemic treatment, a concomitant therapy with systemic immune suppression, up to 5 mg/d prednisolone equivalent is allowed
- •Patients with severely reduced liver function (Child-Pugh Class C)
- •Known allergy or hypersensitivity reaction to ruxolitinib
- •Pregnancy and lactation
- •Any other serious or unstable medical condition that, in the Investigator's judgment, would compromise participant safety or interfere with study conduct; an active infection requiring systemic antimicrobial, antiviral, or antifungal therapy within 14 days before enrolment; or known HIV infection, active hepatitis B (HBsAg positive or detectable HBV DNA), or active hepatitis C (detectable HCV RNA)
- •Thrombocytopenia (platelet count <100,000/microL) or neutropenia (absolute neutrophil count <1000/mcroL)
- •Any condition that would require postponement of the planned curative surgical resection to accommodate the neoadjuvant ruxolitinib period (neoadjuvant cohort)
- •Anticipated inability to observe the minimum treatment-free interval of at least 48 hours between the last ruxolitinib dose and surgery (neoadjuvant cohort)
研究组 & 干预措施
R/M cohort
Patients with recurrent or metastatic (R/M) HNSCC receiving the immune checkpoint inhibitor pembrolizumab who are found to have an increased pretreatment neutrophil-to-lymphocyte ratio (NLR) receive additional intermittent treatment with ruxolitinib tablets twice daily during weeks 6-12 of pembrolizumab treatment. Pembrolizumab is administered according to local standard of care
干预措施: Ruxolitinib (Drug)
R/M cohort
Patients with recurrent or metastatic (R/M) HNSCC receiving the immune checkpoint inhibitor pembrolizumab who are found to have an increased pretreatment neutrophil-to-lymphocyte ratio (NLR) receive additional intermittent treatment with ruxolitinib tablets twice daily during weeks 6-12 of pembrolizumab treatment. Pembrolizumab is administered according to local standard of care
干预措施: Pembrolizumab (Drug)
Neoadjuvant Cohort
Patients with curative locally advanced HNSCC receiving the immune checkpoint inhibitor pembrolizumab who are found to have an increased pretreatment neutrophil-to-lymphocyte ratio (NLR) receive additional intermittent treatment with ruxolitinib tablets twice daily from week 3 to week 5 of neoadjuvant pembrolizumab treatment. Pembolizumab will be administered as per standard of care at the local site.
干预措施: Pembrolizumab (Drug)
Neoadjuvant Cohort
Patients with curative locally advanced HNSCC receiving the immune checkpoint inhibitor pembrolizumab who are found to have an increased pretreatment neutrophil-to-lymphocyte ratio (NLR) receive additional intermittent treatment with ruxolitinib tablets twice daily from week 3 to week 5 of neoadjuvant pembrolizumab treatment. Pembolizumab will be administered as per standard of care at the local site.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
6-Month Progression-Free Survival Rate (R/M cohort only)
时间窗: 6 months after enrollment
Progression-free survival is defined as the time from enrollment to the first documented disease progression or death from any cause, whichever occurs first. The outcome measure is the proportion of participants who are alive and progression-free 6 months after enrollment.
次要结局
- Change in systematic inflammation (Neutrophil-to-Lymphocyte Ratio, NLR)(R/M cohort: at screening within 21 days before start of ruxolitinib or at week 6 (baseline) and at week 12. Neoadjuvant cohort: at screening within 21 days before start of ruxolitinib or at week 3 (baseline), at week 5 and at week 12.)
- Adherence to Planned JAK-Inhibition Treatment (R/M cohort only)(From initiation of ruxolitinib treatment to Week 12 (up to 6 weeks of treatment).)
- Tumour response (R/M cohort only)(Week 12)
- Overall survival (R/M cohort only)(From enrollment until death from any cause or until the end of study follow-up (up to approximately 5 years).)
- Quality of Life Assessed by EORTC QLQ-C30 (R/M cohort only).(At screening, week 12 and week 18)
- Quality of Life Assessed by EORTC QLQ-H&N43 (R/M cohort only)(At screening, week 12, week 18)