A Phase 1, Open-Label, Dose Escalation and Dose Expansion Study to Assess the Safety and Efficacy of Nitric Oxide Injection Into Unresectable Solid Cutaneous/Subcutaneous Primary or Metastatic Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 38
- 试验地点
- 4
- 主要终点
- Incidence of AEs, SAEs and DLTs (safety) parameters.
研究概览
简要总结
This is a Phase 1, open-label, dose-escalation and dose-expansion study comprised of a screening period, a single treatment session, an evaluation period of 21±3 days, and safety and survival follow-up period of up to 12 weeks post-treatment.
详细描述
The purpose of this Phase 1 study is to initiate clinical development of gNO in patients with unresectable cutaneous or subcutaneous primary or metastatic solid tumors that are not amenable or have failed standard treatment, for which no therapy of proven efficacy exists, or which has progressed despite standard therapy. This study of gNO treatment will consist of 2 parts: a dose-escalation part to establish a safe and tolerable dose of gNO in patients with primary or metastatic unresectable cutaneous or subcutaneous solid tumors (Part A), and a dose expansion phase (Part B) which may be initiated at the Sponsor's discretion after the maximum tolerated dose (MTD) and/or optimal biological dose (OBD) (or recommended Phase 2 dose [RP2D]) has been determined in the dose-escalation phase (Part A). This study will be the basis for future studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Patient (male or female) is at least 18 years of age at the time of signature of the informed consent form.
- •Patient has an ECOG Performance Status score of 0-3 and with a life expectancy of ≥3 months.
- •Patient must have a confirmed diagnosis of at least one unresectable cutaneous or subcutaneous histologically confirmed primary or metastatic solid tumor. Up to five target lesions may be identified.
- •No therapy of proven efficacy exists for the tumor, the tumor is not amenable to standard therapies, the tumor has failed to respond to standard therapy or has progressed despite standard therapy.
- •Patient has measurable disease on imaging based on RECIST Version 1.
- •Patient have adequate hematologic and organ function.
- •Patient have not had radiotherapy to the targeted lesions within the preceding 12 months.
- •Superficial tumor axis minimum length and depth of 4.5mm. .
- •Patient is not with childbearing potential or agrees to use adequate contraceptive methods
排除标准
- •The tumor is situated in the lymph node, in thyroid, close to trachea or in facial area or other region which, in the Investigator's opinion, can pose extra risk to the patient.
- •Has received prior systemic anti-cancer therapy including investigational agents within 14 days of the start of study treatment.
- •Active central nervous system tumors or metastases..
- •Received systemic corticosteroid therapy ≤1 week prior to study treatment or any other form of systemic immunosuppressive medication for medically significant acute or chronic conditions.
- •Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, neuropathy and protocol-defined laboratory values.
- •Active or prior documented autoimmune or inflammatory disorders.
- •History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of enrolment.
- •Known active infection and uncontrolled intercurrent illness.
- •Receiving drugs that have contraindication with NO.
- •Patient is receiving anticoagulants including low molecular weight heparin.
研究组 & 干预措施
Cohort 2
Subjects will receive 50,000 ppm NO
干预措施: Nitric Oxide 50,000 ppm (Drug)
Cohort 1
Subjects will receive 25,000 ppm NO
干预措施: Nitric Oxide 25,000 ppm (Drug)
Cohort 3
Subjects will receive 100,000 ppm NO
干预措施: Nitric Oxide 100,000 ppm (Drug)
RP2D Expansion
Subjects will receive the RP2D dose of NO
干预措施: Nitric Oxide selected dose (Drug)
结局指标
主要结局
Incidence of AEs, SAEs and DLTs (safety) parameters.
时间窗: up to12 weeks from injection
The incidence and characteristics of adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs) and changes in assessed safety parameters. Toxicity will be graded according to NCI CTCAE version 5.0
次要结局
- Anti-tumor activity of a single intratumoral gNO injection at all administered doses(up to Day 21 from injection)