A Dose Escalation and Dose Expansion Study of NOX66 Plus Doxorubicin in Anthracycline-naïve, Adult Patients With Soft Tissue Sarcoma - CEP-2
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 4
- 主要终点
- Dose Escalation: Number of Patients With Dose-limiting Toxicities (DLTs)
研究概览
简要总结
This is a Phase I, open-label, dose-escalation and dose-expansion study of NOX66 given rectally, in cohorts of patients with metastatic soft tissue sarcoma (STS) who have not been exposed to anthracycline therapy, using a fixed dose-escalation schema every 21 days to establish the maximum tolerated dose (MTD) of the combination of NOX66 and doxorubicin.
详细描述
The study will contain dose-escalation cohorts and dose-expansion cohorts. The study design allows an exploration of different doses of NOX66 with safety monitoring to ensure the safety of the patients.
Dose-escalation cohorts: It will include three planned Treatment Groups (800, 1200, 1800 mg daily) and patients enrolled in these groups will receive 7 days of monotherapy treatment with NOX66 followed by a 5-day washout period. Thereafter, patients will enter a combination therapy (only if no significant toxicity is observed during monotherapy). This will commence with Cycle 1, which will consist of 7 days of NOX66, and on Day 2 of the 21-day cycle, doxorubicin will be administered. Patients will continue to be treated for up to 6 x 21-day cycles of NOX66 and doxorubicin. New patients will be entered at the next dose level of NOX66, if no dose-limiting toxicities have occurred among the first 3 patients at the end of cycle 1. During the dose-escalation, MTD of the combination of NOX66 and doxorubicin will be determined.
Dose-expansion cohort: On completion of the dose-escalation cohort, patients will be enrolled into a dose-expansion at the MTD of the combination of NOX66 and doxorubicin. All patients will enter directly into 21-day combination cycles and will be given NOX66 therapy for 7 days and doxorubicin will be administered on Day 2 of each cycle. Treatment will be terminated upon disease progression, unacceptable toxicity, or a maximum of 6 cycles.
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
- •Adult patients with a histologically confirmed diagnosis of metastatic or recurrent soft tissue sarcoma
- •Patients for whom treatment with doxorubicin is considered to be appropriate
- •Left ventricular ejection fraction ≥ 50%
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Disease that is considered measurable according to RECIST v1.1.
排除标准
- •Histologically or cytologically confirmed Kaposi's sarcoma, gastrointestinal stromal tumor (GIST), extra-skeletal myxoid chondrosarcoma, epithelioid hemangioendothelioma, and desmoid tumor
- •Untreated metastases to the central nervous system
- •Received previous treatment with anthracyclines and anthracenediones
- •Previous radiation therapy to the mediastinal or pericardial area
- •A known allergy to any of the treatment components
- •Patient not willing to use suppositories
- •Patients with a colostomy
- •Patients who have had a colectomy (total or left hemicolectomy) with re-anastomosis
- •Patients for whom administration of the suppositories are likely to cause pain (e.g., inflamed hemorrhoids, fissures, or lesions of the anus or rectum)
- •Patients with fecal impaction, chronic idiopathic constipation, or chronic diarrhea or alternating irritable bowel disease
- •Patients with inflammatory bowel disease
- •Previous treatment with an investigational agent or the non-approved use of a drug or device within 4 weeks before study entry
- •Uncontrolled diabetes mellitus
- •Patients who require concomitant use of strong inhibitors or inducers of CYP3A4, CYP2D6 or P- glycoprotein (P- gp)
研究组 & 干预措施
Dose-Escalation Cohort 1: NOX66 800 mg + Doxorubicin
干预措施: NOX66 (Drug)
Dose-Escalation Cohort 1: NOX66 800 mg + Doxorubicin
干预措施: Doxorubicin (Drug)
Dose-Escalation Cohort 2: NOX66 1200 mg + Doxorubicin
干预措施: NOX66 (Drug)
Dose-Escalation Cohort 2: NOX66 1200 mg + Doxorubicin
干预措施: Doxorubicin (Drug)
Dose-Escalation Cohort 3: NOX66 1800 mg + Doxorubicin
干预措施: NOX66 (Drug)
Dose-Escalation Cohort 3: NOX66 1800 mg + Doxorubicin
干预措施: Doxorubicin (Drug)
Dose-Expansion Cohort: NOX66 + Doxorubicin
干预措施: NOX66 (Drug)
Dose-Expansion Cohort: NOX66 + Doxorubicin
干预措施: Doxorubicin (Drug)
结局指标
主要结局
Dose Escalation: Number of Patients With Dose-limiting Toxicities (DLTs)
时间窗: Cycle 1 of each dose (Cycle length is 21 days)
Determination of the MTD of NOX66 in combination with doxorubicin. MTD is defined as the dose level at which no more than 1 patient out of 6 experiences a DLT at the end of Cycle 1.
Number of Patients With Adverse Events (AEs) for NOX66
时间窗: From first study treatment with DOX66 monotherapy through study completion, approximately of 14 months and 20 days. From February 11, 2022, to May 1, 2023
Characterization of the safety and tolerability of NOX66.
次要结局
未报告次要终点