A Phase I, Open-label, Two-cohort Study of Recombinant Human Endostatin Adenovirus in Combination With Immune Checkpoint Inhibitors in Patients With Recurrent or Metastatic Head and Neck Cancer or Esophageal Squamous Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Incidence of treatment-related adverse effects (TRAEs)
研究概览
简要总结
This is a Phase I, open-label, dual-cohort clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of intratumoral injection of recombinant human endostatin adenovirus in combination with a PD-1 inhibitor in patients with recurrent or metastatic head and neck cancer, or in patients with esophageal squamous cell carcinoma (ESCC) with superficial lymph node metastasis.
详细描述
Cohort A will enroll patients with recurrent or metastatic head and neck cancer. Cohort B will enroll patients with ESCC with superficial lymph node metastasis. Both cohorts will receive intratumoral injection of recombinant human endostatin adenovirus combined with intravenous an immune checkpoint inhibitor.
The primary objectives are to assess the safety profile, incidence of dose-limiting toxicities (DLTs), and treatment-related adverse events (TRAEs) of the combination therapy. The secondary objectives include evaluation of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Each cohort plans to enroll approximately 20 patients, with a total of 40 participants.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Cohort A (Head and Neck Cancer): ≤70 years
- •Cohort B (Esophageal Squamous Cell Carcinoma): ≤75 years
- •Histologically or cytologically confirmed recurrent or metastatic:
- •Cohort A: Head and Neck Cancer
- •Cohort B: ESCC, AJCC 9th edition stage IV
- •Prior treatment:
- •Cohort A: ≥1 prior platinum-based chemotherapy regimen or platinum-refractory/intolerant
- •Cohort B: Prior immune checkpoint inhibitor (ICI) therapy with documented acquired resistance after prior PR or SD
- •At least one lesion accessible for intratumoral injection
- •Cohort A: measurable lesion ≥2 cm by RECIST 1.1
- •Cohort B: superficial metastatic lymph nodes (cervical or supraclavicular)
- •ECOG performance status
- •Cohort A: 0-2
- •Cohort B: 0-1
- •Adequate organ function
- •Life expectancy ≥12 weeks (Cohort A)
- •No anti-tumor therapy (chemotherapy, radiotherapy, biotherapy, antiviral) within 4 weeks prior to enrollment (Cohort A)
- •Availability of fresh tumor tissue specimen or pathological slides from the injection target lesion (Cohort B)
- •Male/female patients of childbearing potential must use effective contraception during study and for at least 6 months after treatment
- •Voluntary participation with signed informed consent
排除标准
- •Known allergy or hypersensitivity to study drugs
- •Lesions unsuitable for injection due to proximity to major blood vessels, nerves, or hollow organs, or with extensive necrosis
- •Deeply located lesions with high procedural difficulty (Cohort B)
- •Concurrent radiotherapy to target lesion(s) (Cohort A)
- •Prior anti-angiogenic therapy (Cohort A)
- •Immunosuppressive therapy or systemic corticosteroids >10 mg/day prednisone (or equivalent) within 2 weeks prior to enrollment
- •Active autoimmune disease or history of autoimmune disease
- •Congenital or acquired immunodeficiency
- •Severe coagulopathy, bleeding tendency, or high-risk lesions (Cohort B)
- •Poor nutritional status (Cohort B)
- •Interstitial lung disease with symptoms or radiographic evidence (Cohort B)
- •Severe uncontrolled systemic disease or recent myocardial infarction (<3 months)
- •Acute infection
- •Pregnancy or breastfeeding
- •Other malignancy besides ESCC (Cohort B)
- •Patients unlikely to comply with follow-up or participation requirements
- •Any condition deemed unsuitable for enrollment by the investigator
研究组 & 干预措施
Endostatin Adenovirus+PD-1 inhibitor
Recombinant Human Endostatin Adenovirus: Administered via intratumoral injection twice every 3 weeks for a total of eight doses, or until disease progression, the occurrence of unacceptable toxicity, or death from any cause, whichever occurs first. Immune checkpoint inhibitor: Administered via intravenous infusion once every 3 weeks.
(This study includes two parallel cohorts: Cohort A (recurrent/metastatic head and neck cancer) and Cohort B (esophageal squamous cell carcinoma). Both cohorts will receive the same intervention.)
干预措施: recombinant human endostatin adenovirus (Biological)
Endostatin Adenovirus+PD-1 inhibitor
Recombinant Human Endostatin Adenovirus: Administered via intratumoral injection twice every 3 weeks for a total of eight doses, or until disease progression, the occurrence of unacceptable toxicity, or death from any cause, whichever occurs first. Immune checkpoint inhibitor: Administered via intravenous infusion once every 3 weeks.
(This study includes two parallel cohorts: Cohort A (recurrent/metastatic head and neck cancer) and Cohort B (esophageal squamous cell carcinoma). Both cohorts will receive the same intervention.)
干预措施: PD-1 Inhibitor (Drug)
结局指标
主要结局
Incidence of treatment-related adverse effects (TRAEs)
时间窗: Through study completion, an average of 1.5 year
This study will collected any adverse medical events that occurred during the study drug treatment, and the treatment related adverse events as assessed by CTCAE v5.0.
Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: During the first cycle of treatment （21 days）
DLTs are defined as treatment-related adverse events occurring during the DLT evaluation period that meet protocol-specified criteria for severity and duration, as assessed by NCI CTCAE v5.0.
次要结局
- Objective Response Rate (ORR)(up to 12 months)
- Disease Control Rate (DCR)(up to 12 months)
- Progression-Free Survival (PFS)(up to 12 months)
- Overall Survival (OS)(up to 24 months)
研究者
Zhen-Yu Ding
Clinical Professor
Sichuan University