Phase II Study of ADI-PEG 20 in Patients With Relapsed Sensitive or Refractory Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 22
- 试验地点
- 8
- 主要终点
- Best Overall Response
研究概览
简要总结
This was a 2-arm, open-label, phase 2 study of pegylated arginine deiminase (ADI-PEG) 20 in subjects with relapsed sensitive or refractory small cell lung cancer (SCLC). ADI-PEG 20 was administered intramuscularly (IM) at a fixed dose of 320 IU/m^2 once weekly for a 4-week cycle. The primary objective was to assess clinical efficacy with a primary endpoint of tumor response by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 after 4 weeks. Secondary objectives were to assess the safety, pharmacodynamics, and immunogenicity of ADI-PEG 20, as well as clinical efficacy with a secondary endpoint of overall survival.
详细描述
Subjects were enrolled sequentially (non-randomized) into two separate cohorts in parallel. Cohort 1 comprised subjects with "sensitive" disease and Cohort 2 comprised subjects with "refractory" disease. Both cohorts received the same treatment regimen consisting of 4 weekly IM administrations of ADI-PEG 20 (320 IU/m^2), followed by a 1-week follow-up (1 cycle). No dose adjustment was allowed. Additional treatment cycles were permitted in the absence of disease progression requiring other therapeutic interventions.
Each cohort was to be enrolled in 2 stages. In the first stage, 15 subjects were to be accrued in Cohort 1 and 12 subjects in Cohort 2. If ≥ 3 subjects met the primary endpoint in Cohort 1, then an additional 13 subjects were to be accrued in the second stage. If ≤ 2 subjects met the primary endpoint in Cohort 1, then the study was to be terminated and declared negative for Cohort 1. If ≥ 1 subject met the primary endpoint in Cohort 2, then an additional 4 subjects were to be accrued in the second stage. If no subjects met the primary endpoint in Cohort 2, then the study was to be terminated and declared negative. Additionally, if at any time a death or two grade 4 adverse events (AEs) that were definitely related or probably related to the study drug occurred, then the study was to be stopped.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have had histologically documented SCLC
- •Assigned to one of two cohorts based on the following characteristics: Cohort 1: "Sensitive" disease subjects who had 1 previous line of chemotherapy and maintained an appropriate response for 90 days or more; or Cohort 2: "Refractory" disease subjects, who had (a) 1 previous line of chemotherapy and either had no response or progressed in less than 90 days after completing treatment or (b) any subject ("sensitive" or "refractory") in need of third-line therapy, i.e., who completed or failed 2 previous lines of chemotherapy
- •Measurable disease using RECIST version 1.1
- •Argininosuccinate synthetase (ASS) tumor expression was either negative or < 5% + tumor cells by immunohistochemistry analysis
- •Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2
- •Laboratory parameters for vital functions in the normal range. Laboratory abnormalities that were not clinically significant were generally permitted, except for the following laboratory parameters, which were to be within the ranges specified:
- •Neutrophil count: ≥ 1.5 x 10^9/L
- •Lymphocyte count: ≥ 0.5 x 10^9/L
- •Platelet count: ≥ 50 x 10^9/L
- •Serum creatinine: ≤ 1.5 x upper limit of normal (ULN) (or creatinine clearance ≥ 60 mL/min)
- •Serum bilirubin: ≤ 2 mg/dL (or ≤ 34 µmol/L)
- •Serum uric acid: ≤ 8 mg/dL (or ≤ 0.48 mmol/L)
- •International normalized ratio (INR): ≤ 1.5
- •Partial thromboplastin time: ≤ 1.5 x ULN
- •Age ≥ 18 years
- •Able and willing to give valid written informed consent
排除标准
- •Previous treatment with ADI-PEG 20
- •Known allergy to pegylated products
- •History of uncontrolled seizures
- •Serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders, or any condition that in the opinion of the Investigator would interfere with the ability of the patient to fulfill the study requirements
- •Metastatic disease to the central nervous system, unless treated and stable
- •Known immunodeficiency or human immunodeficiency virus (HIV) positivity
- •Participation in another clinical trial involving another investigational agent within 3 weeks prior to first dosing of study agent
- •Any other malignancy that required protocol-specified restricted concomitant therapy
- •Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study
- •Lack of availability for clinical follow-up assessment
- •Pregnancy or breast feeding
- •Refusal or inability to use effective means of contraception for men and women of childbearing potential for the duration of the study
研究组 & 干预措施
Cohort 1: Sensitive Disease
Cohort 1 comprised subjects with "sensitive" disease, defined as subjects who were treated with 1 previous line of chemotherapy and maintained an appropriate response for 90 days or more. Subjects received 4 administrations of ADI-PEG 20 (320 IU/m^2) followed by 1 week of follow-up in each treatment cycle.
干预措施: ADI-PEG 20 (Arginine deiminase pegylated) (Drug)
Cohort 2: Refractory Disease
Cohort 2 comprised subjects with "refractory" disease, defined as subjects who either (a) were treated with 1 previous line of chemotherapy and either had no response or progressed < 90 days after completing treatment or (b) required third-line therapy, i.e., had completed 2 previous lines of chemotherapy, regardless of response. Subjects received 4 administrations of ADI-PEG 20 (320 IU/m^2) followed by 1 week of follow-up in each treatment cycle.
干预措施: ADI-PEG 20 (Arginine deiminase pegylated) (Drug)
结局指标
主要结局
Best Overall Response
时间窗: Every 4 to 8 weeks for up to 16 weeks
Tumor responses were evaluated using any appropriate imaging type and were categorized according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Per RECIST for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions \[no evidence of disease\]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.
次要结局
- Assessment of Immunogenicity of ADI-PEG 20(Every 1 to 4 weeks for up to 16 weeks)
- Assessment of Safety of Arginine Deiminase Pegylated (ADI-PEG) 20(Every 1 to 4 weeks for up to 16 weeks)
- Assessment of Pharmacodynamics of ADI-PEG 20(Every 1 to 4 weeks for up to 16 weeks)
- Assessment of Overall Survival(Every 4 weeks for up to 16 months)