A Phase 1b Trial in Relapsed/Refractory Small Cell Lung Cancer to Determine the Clinical Activity, Safety Profile, and Pharmacology of ST-001, a Fenretinide Phospholipid Suspension (12.5 mg/mL) for Intravenous Infusion
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 44
- 试验地点
- 2
- 主要终点
- To determine the MTD of ST-001 (12.5mg/mL) for IV infusion in patients with SCLC
研究概览
简要总结
This study evaluates a fenretinide phospholipid suspension for the treatment of small cell lung cancer (SCLC).
详细描述
Fenretinide has been shown to be a relatively safe and effective anticancer therapy; however, low fenretinide bioavailability and dose limiting toxicities due to excipients used in previous formulations has impeded its therapeutic utility. The product formulation in the current study (ST-001) is a phospholipid suspension of nanoparticle sized fenretinide. The current study is a Phase 1 trial in in relapsed/refractory small cell lung cancer to determine the clinical activity, safety profile, and pharmacology of ST-001.
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
- •Small cell lung cancer (SCLC).
- •Patients must all have at least one measurable disease site using RECIST version 1.1 criteria.
- •Patients must have relapsed or refractory disease to prior treatment with platinum-based chemotherapy ± immunotherapy. There is no limit on the number of prior systemic treatment regimens.
- •Relapsed/refractory disease of any stage if incurable in nature, is eligible for enrollment.
- •Minimum of 3 weeks or 5 half-lives, whichever is shorter must have elapsed since last systemic treatment. A 1-week washout is required for palliative radiation treatment and 2-week washout is required for whole brain radiation treatment. Patients must have recovered from all clinically significant toxicity of last treatment and cleared the pharmacological agent(s) used previously.
- •ECOG performance status 0-1 (Karnofsky ≥60%).
- •Life expectancy greater than 6 months.
- •Patients must have normal organ and marrow function.
- •Triglyceride blood level (fasting) <300mg/dL at time of enrollment (normal: <150mg/dL; borderline high = 150-199mg/dL; high = 200-499mg/dL; very high = 500mg/dL or higher).
- •Women of non-child bearing potential, that is women who have been menopausal or surgically sterile for more than 1 year, are eligible for enrolment in the study.
- •Informed consent of the patient or a legal authorized representative (LAR) must be obtained prior to any study related procedures.
排除标准
- •Mixed SCLC/NSCLC tumors are not eligible. Pregnant or breastfeeding women cannot take part in this study. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- •Patients who are receiving any other investigational agents. SCLC patients with history of CNS metastasis may be included if CNS disease is asymptomatic and controlled without progression at least 4 weeks after treatment with radiotherapy, and patient is either no longer taking corticosteroids or on a stable dose of corticosteroids.
- •History of allergic reactions or sensitivity to retinoids or to any excipients of ST-
- •Patients who require concurrent treatment with drugs that are strong CYP3A inducers are excluded from the trial.
- •Patients who require concurrent treatment with drugs that are strong to moderate CYP3A inhibitors are excluded from the trial.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (NY heart classification III/IV), unstable angina pectoris, cardiac arrhythmia, QTc interval >450 milliseconds for men and >460 milliseconds for women on baseline triplicate ECG, or psychiatric illness/social situations that would limit compliance with study requirements.
- •HIV-positive patients on combination antiretroviral therapy are ineligible. Patients with any active hepatitis infections. Presence of nyctalopia (night blindness), or hemeralopia (defective vision in a bright light, 'day blindness') at enrollment, or any other retinal, ophthalmological condition (e.g.: retinitis pigmentosa, choroidoretinitis and xerophthalmia), and glaucoma.
- •History of solid tumor malignancy other than the diseases under study, diagnosed within the last three (3) years of study enrollment, excluding adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer, in situ breast cancer, in situ prostate cancer (patients must have shown no evidence of active disease for 2 years prior to enrollment).
研究组 & 干预措施
Expanded Phase 1b
Expansion of the dose-finding Phase 1a to determine the safety and maximum tolerated dose (MTD) of the investigative drug product (ST-001).
干预措施: Fenretinide (Drug)
Standard Phase 1a
During the Standard Phase 1a, three patients are enrolled into each dose level cohort and the three patients must be evaluated for cycle 1 toxicity before the decision can be made to open the next higher dose level.
干预措施: Fenretinide (Drug)
结局指标
主要结局
To determine the MTD of ST-001 (12.5mg/mL) for IV infusion in patients with SCLC
时间窗: From enrollment to end of treatment is 3 weeks
To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of ST-001 12.5 mg/mL for IV infusion (ST-001) in patients with Relapsed/Refractory SCLC when ST-001 is administered via 4-hour IV infusion daily for five consecutive days, q3weeks. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in \>33% of participants. DLTs are defined as any treatment-related Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0) Grade 3 or 4 adverse events.
To evaluate the progression-free survival (PFS) of patients with relapsed or refractory small-cell lung cancer (SCLC) who are treated with ST-001 after receiving at least one prior systemic therapy.
时间窗: From enrollment to end of treatment is 3 weeks
Evaluate progression-free survival (PFS) in patients with relapsed or refractory small-cell lung cancer (SCLC) after prior platinum-based chemotherapy ± immunotherapy who are treated with ST-001 (12.5mg/mL) for IV Infusion, using a Simon 2-stage study design with an interim analysis for futility. PFS is defined as the time from start of treatment to disease progression (increase in tumor size, new metastases) or death.
次要结局
- To describe the toxicity profile of ST-001 in patients with SCLC(From enrollment to end of treatment is 3 weeks)
- Objective Response Rate (ORR)(From enrollment to end of treatment is 3 weeks)
- Progression-free survival (PFS)(From enrollment to end of treatment is 3 weeks)
- Cmax(From enrollment to end of treatment is 3 weeks)
- Tmax(From enrollment to end of treatment is 3 weeks)
- Vd(From enrollment to end of treatment is 3 weeks)
- t½(From enrollment to end of treatment is 3 weeks)
- To observe and record anti-tumor activity of ST-001 in patients with SCLC(From enrollment to end of treatment is 3 weeks)
- To describe the pharmacokinetics of fenretinide when ST-001 is administered by daily infusion for 5 consecutive days every 3 weeks.(From enrollment to end of treatment is 3 weeks)