Phase 2 Clinical Trial to Evaluate Efficacy and Safety of SM-88 Used With Methoxsalen, Phenytoin, and Sirolimus (MPS) as Maintenance Therapy Following Standard Treatments for Ewing's Sarcoma or as Salvage Therapy for Advanced Sarcomas
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Overall Response Rate
研究概览
简要总结
The primary objective is to evaluate the efficacy of SM-88, a combination metabolic cancer treatment, in two study cohorts:
- Clinically advanced Ewing's Sarcoma patients who have not progressed at the conclusion of systemic treatment
- Clinically advanced sarcoma patients in the salvage treatment setting
Up to 24 efficacy evaluable patients (up to 12 per cohort) will be enrolled. Study patients will receive oral SM-88, with scheduled safety and efficacy evaluations.
详细描述
This prospective, open-label, two stage, pilot phase 2 trial evaluates the efficacy and safety of SM-88 in two cohorts of patients: 1) as maintenance therapy following standard primary or palliative treatments for Ewing's sarcoma patients with high risk of relapse or disease progression; and 2) as salvage therapy for patients with clinically advanced sarcomas.
The primary objective is to evaluate the efficacy of SM-88, a combination metabolic cancer treatment, measured as positive efficacy events, including overall response, maintaining stable disease for ≥ 3 months, or progression free survival at least 1.5 times longer than the last prior line of treatment.
Eligible patients will receive daily oral treatment with SM-88, which consists of D,L-alpha-metyrosine, used with methoxsalen, phenytoin, and sirolimus in continuous treatment cycles of 28 days. Treatment will continue until: 1) Symptomatic, clinical progression with radiographic progressive disease; 2) 48 weeks after documented complete response; or 3) evidence of unacceptable toxicity, or other decision to discontinue treatment
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to understand and willingness to provide written informed consent to participate in this study
- •≥12 years of age
- •Maintenance treatment cohort: Histologic or cytologic diagnosis of Ewing's sarcoma, including non-resected, locally advanced or metastatic disease
- •Salvage treatment cohort: Non-resected, locally advanced or metastatic sarcoma (including Ewing's sarcoma) for which there is no standard of care treatment and no curative other option
- •Radiographic disease assessment within 35 days prior to enrollment and planned treatment start with study drug
- •Prior treatment:
- •Maintenance treatment cohort : 1-3 prior lines of systemic treatment (including current treatment)
- •Salvage cohort: Any number of prior treatments
- •Maintenance treatment cohort only: Patient completed current line of treatment (systemic, surgery, radiation) prior to enrollment, without disease progression as compared to baseline AND has achieved at least one of the following
- •CR in response to current second or third line treatment
- •PR in response to current line of treatment (after at least 4 cycles, if treatment included systemic therapy)
- •SD in response to current line of treatment (after at least 4 cycles, if treatment included systemic therapy)
- •Measurable disease, except for patients in Cohort A who have achieved CR at the conclusion of current 2nd or 3rd line of treatment
- •ECOG performance status 0-2
- •Adequate organ function defined as all laboratory parameters ≤ Grade 2 NCI CTCAE criteria
- •Patients must be able to swallow and retain whole capsules
排除标准
- •Systemic anticancer agents within 14 days prior to treatment on study
- •Major surgery within 30 days
- •Prior treatment with SM-88
- •Any screening laboratory, electrocardiogram (ECG), other clinical finding, comorbidity or clinical history that, in the opinion of the investigator, indicates an unacceptable risk for patient to participate in the study or would limit patient's ability to comply with study requirements
- •History of any drug allergies or significant adverse reactions to any of the components of SM-88
- •History of light sensitive diseases for which methoxsalen would be contraindicated
- •Current or anticipated treatment with a contraindicated medication
- •Evidence of viral infections including human immunodeficiency virus (HIV), hepatitis B, and hepatitis C
研究组 & 干预措施
Maintenance Treatment: Ewing's Sarcoma
Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus
干预措施: Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS) (Drug)
Salvage Treatment: Sarcoma
Combination metyrosine-derivative, low-dose methoxasalen, phenytoin and sirolimus
干预措施: Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS) (Drug)
结局指标
主要结局
Overall Response Rate
时间窗: Every 3 months for up to 2 years
Complete response (CR) + partial response (PR) as evaluated using RECIST 1.1
Stable Disease for at Least 3 Months
时间窗: Every 3 months for up to 2 years
Stable disease (SD) as evaluated using RECIST 1.1
Progression Free Survival on Study of at Least 1.5 Times the Duration of PFS for the Last Prior Treatment
时间窗: Every 3 months for up to 2 years
From date of enrollment until the date of first documented progression, as evaluated using RECIST 1.1, or date of death, whichever occurs first
次要结局
- Duration of Response(Every 3 months for up to 2 years)
- Overall Survival(Every 3 months for up to 2 years)
- Clinical Benefit Rate(Every 3 months for up to 2 years)
- Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5(From date of enrollment until 28 days after last treatment with SM-88)