A Phase I/II Study of Nal-IRI (ONIVYDE® ) and Carboplatin in Patients With Advanced or Metastatic Gastroenteropancreatic Poorly Differentiated Neuroendocrine Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 52
- 试验地点
- 6
- 主要终点
- MTD and RP2D
研究概览
简要总结
The current study is an investigator-initiated, single-arm phase 1/2 study that enrolled patients with advanced or recurrent and/or metastatic gastroenteropancreatic poorly differentiated neuroendocrine carcinoma for the treatment of nal-IRI (ONIVYDE®) plus carboplatin as the first-line chemotherapy.
详细描述
Eligible patients will be treated into two cohorts.
In adaptive phase 1 cohort:
Six patients will be enrolled in safety run-in cohort of dose level 0. If less than 2 patients experience dose-limiting toxicity (DLT) in dose level 0, dose level 1 will be tested. However, if more than 1 patients experience DLT in dose level 0, dose level -1 will be tested. The MTD at which no more than 1 of the 6 patients experience DLT will be determined for the phase 2 cohort. Otherwise, additional 6 patients will be tested in the dose level -1. Based on results from safety run-in cohort, PR2D will be determined. The evaluable patients in RP2D cohort will be incorporated into phase 2 cohort for final analysis.
Dose in phase 1 cohort:
Dose level 1= onivyde 100 mg/m2 plus carboplatin AUC=4, intravenously both on day 1, q3wk Dose level 0= onivyde 80 mg/m2 plus carboplatin AUC=4, intravenously both on day 1, q3wk Dose level -1= onivyde 60 mg/m2 plus carboplatin AUC=4, intravenously both on day 1, q3wk Carboplatin dose (mg) is calculated by the Calvert formula: AUC x (eGFR + 25). Cockcroft-Gault equation: eGFR (calculated Ccr)= [(140-age) x weight x 0.85 (if female)] / (72 x serum Cr). The maximum eGFR for dose calculation is 125 ml/min.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •histologically confirmed locally advanced or metastatic gastroenteropancreatic poorly differentiated neuroendocrine carcinoma.
- •patients either are chemotherapy-naive or had received adjuvant chemotherapy > 6 months before recurrence.
- •at least one measurable lesion according to the RECIST version 1.1..
- •patients were aged 20 to 80 years with ECOG performance status of 0 to
- •patients had a life expectancy ≥ 3 months.
- •patients had adequate renal function with defined as serum creatinine ≤ 2 times the upper limit of normal (ULN) or eGFR (calculated Ccr) ≥ 45 mL/min.
- •patients had adequate hepatic function, defined as total bilirubin ≤ 1.5 times the ULN and alanine aminotransferase ≤ 2.5 the ULN and ≤ 5 times the ULN within the setting of liver metastases.
- •patients had adequate bone marrow function, defined as an absolute neutrophil count ≥ 1500/mm3, platelet count ≥ 100,000/mm3, and hemoglobin ≥ 9 g/dL.
- •Normal ECG or abnormal ECG without any clinical significantly findings.
- •Able to understand and sign an informed consent (or have a legal representative who is able to do so).
排除标准
- •a history of palliative chemotherapy or disease recurrence < 6 months from the time of last adjuvant chemotherapy and/or radiotherapy.
- •known hypersensitivity to liposome product, irinotecan or carboplatin.
- •receipt of major surgery within the past 4 weeks before study enrollment.
- •With clinically significant gastrointestinal disorder including bleeding, inflammation, occlusion or diarrhea > grade
- •concurrent severe infection with intravenous systemic antibiotics treatment.
- •severe, uncontrolled medical condition including severe liver disease, heart disease, uncontrolled diabetes or hypertension, or pulmonary disease.
- •another previous malignancy diagnosed within the past 5 years except for nonmelanoma skin cancer or stage I cervical cancer.
- •active CNS metastasis defined by clinical symptoms, cerebral edema, steroid or anti-convulsant requirement, or progressive growth. Patients with a history of CNS metastasis or cord compression are allowed in the study if they have been treated and are clinically stable.
- •psychiatric illness or social situation that would preclude study compliance
- •women with pregnant or breast feeding (a urine pregnancy test must be performed on all patients who are of childbearing potential before entering the study, and the result must be negative).
研究组 & 干预措施
nal-IRI (ONIVYDE®) and Carboplatin
nal-IRI (ONIVYDE®) and Carboplatin
干预措施: nanoliposomal irinotecan plus carboplatin (Drug)
结局指标
主要结局
MTD and RP2D
时间窗: 3 Years
• in phase 1 cohort, to determine MTD (maximum tolerated dose) and recommended phase 2 dose (RP2D)
tumor response rate
时间窗: 3 Years
• in phase 2 cohort, to assess the objective tumor response rate
次要结局
- PFS and OS(3 Years)
- To explore the treatment-related adverse events as assessed by CTCAE v5.0(3 Years)