An Open-Label, Non-controlled, Non-randomized Sequential Design, Drug-Interaction Study of Necitumumab (IMC-11F8) in Combination With Gemcitabine-Cisplatin in Patients With Advanced Solid Cancers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- PK: Dose-Normalized Cmax of Cisplatin
研究概览
简要总结
The purpose of this study is to investigate the pharmacokinetics (PK) of necitumumab in combination with gemcitabine-cisplatin in participants with advanced malignant solid tumors and to assess the potential for drug-drug interactions between necitumumab and gemcitabine-cisplatin.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have documented advanced or metastatic malignant solid tumors (except for colorectal tumors with KRAS mutation) that are resistant to standard therapy or for which no standard therapy is available
- •May have measurable or non-measurable disease
- •Have resolution to Grade 0 or 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE 4.0) of all clinically significant toxic effects (other than alopecia) of prior chemotherapy, surgery, radiotherapy, or hormonal therapy
- •Have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1
- •Have adequate hepatic, hematologic and renal function
- •If female, are surgically sterile, postmenopausal, or agree to be compliant with a highly effective contraceptive method during and for 6 months after the treatment period. If male, are surgically sterile or agree to be compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period
- •Female participants of childbearing potential have a negative serum pregnancy test within 7 days prior to the first dose of study therapy
排除标准
- •Have received a systemic anticancer agent (including EGFR tyrosine kinase inhibitors) or device within 28 days prior to first dose of study therapy
- •The most recent anticancer therapy received by the participant included either gemcitabine or cisplatin (or both)
- •Have received radiotherapy within 14 days prior to first dose of study therapy
- •Have received cytotoxic chemotherapy within 21 days prior to first dose of study therapy
- •Are receiving concurrent treatment with another anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy, radiation therapy, chemoembolization, or targeted therapy
- •Are considered surgical candidates (with resectable disease)
- •Have brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants
- •Have narrowing of or blockage in large veins
- •Have coronary artery disease or uncontrolled congestive heart failure
- •Have uncontrolled angina pectoris, or experienced myocardial infarction within 6 months prior to first dose of study therapy
- •Have an ongoing or active infection (requiring treatment), including active tuberculosis or known infection with the human immunodeficiency virus
- •Have a history of significant neurological or psychiatric disorders, including dementia, seizures, or bipolar disorder
- •Have known drug or alcohol abuse
- •If female, are pregnant or breastfeeding
- •Have had major surgery within 28 days prior to first dose of study medication or subcutaneous venous access device implantation within 7 days prior to first dose of study therapy
- •Are currently enrolled in, or discontinued within the 30 days prior to first dose of study therapy from a clinical trial involving an investigational product or nonapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
研究组 & 干预措施
Necitumumab, Gemcitabine and Cisplatin
The study will be conducted in two sequential periods: a 3-week PK run-in participants will be treated sequentially with single doses of cisplatin, gemcitabine, and necitumumab. Cycle 1 will begin immediately following the PK run-in period.
干预措施: Necitumumab (Biological)
Necitumumab, Gemcitabine and Cisplatin
The study will be conducted in two sequential periods: a 3-week PK run-in participants will be treated sequentially with single doses of cisplatin, gemcitabine, and necitumumab. Cycle 1 will begin immediately following the PK run-in period.
干预措施: Gemcitabine (Drug)
Necitumumab, Gemcitabine and Cisplatin
The study will be conducted in two sequential periods: a 3-week PK run-in participants will be treated sequentially with single doses of cisplatin, gemcitabine, and necitumumab. Cycle 1 will begin immediately following the PK run-in period.
干预措施: Cisplatin (Drug)
结局指标
主要结局
PK: Dose-Normalized Cmax of Cisplatin
时间窗: Run-In Period Day 1 Cohort 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion; Cycle 1, Day 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion
PK: Dose Normalized AUC(0-∞) of Gemcitabine
时间窗: Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Necitumumab
时间窗: Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 Hour (h) Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion
PK: Dose-Normalized Cmax of Gemcitabine
时间窗: Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion
PK: Dose-Normalized AUC(0-24) of Gemcitabine
时间窗: Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion
PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity, (AUC[0-∞]) of Necitumumab
时间窗: Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion; Cycle 1 Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion
PK: Area Under Concentration-Time Curve From Zero to Time 168 (AUC[-168]) of Necitumumab
时间窗: Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion
PK: Dose-Normalized AUC(0-5) of Cisplatin
时间窗: Run-In Period Day 1 Cohort 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion; Cycle 1, Day 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion
次要结局
- Number of Participants With Anti-Necitumumab Antibodies(Baseline through, 30-Day Follow-Up)
- PK: Cmax of Necitumumab After Administration of Process C and Process D Drug Product(Run-In Period Day 3 Cohort 1 and Cohort 2: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion)
- Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) (Antitumor Activity of Necitumumab in Combination With Gemcitabine-cisplatin Chemotherapy)(Baseline to Measured Progressive Disease (Up to 14 Months))
- PK: AUC(0-∞) of Necitumumab After Administration of Process C and Process D Drug Product(Run-In Period Day 3 Cohort 1 and Cohort 2: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion)