A Phase I Trial of Gemcitabine (Gemzar) Plus ABI-007 (ABRAXANE) In Patients With Advanced Metastatic Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 67
- 试验地点
- 5
- 主要终点
- Number of Participants With Dose-limiting Toxicities
研究概览
简要总结
To determine the maximum tolerated dose and dose-limiting toxicity of Gemcitabine plus Albumin-bound paclitaxel (ABI-007) in patients with advanced metastatic pancreatic cancer.
详细描述
Albumin-bound paclitaxel is a novel, solvent-free, albumin-bound, 130 nanometer particle form of paclitaxel designed to avoid the problems associated with solvents used in Taxol(Abraxane prescribing information 2005). Albumin has a number of properties that make it an attractive molecule to combine with paclitaxel. Albumin is a natural transporter of endogenous hydrophobic molecules such as water-insoluble vitamins and hormones (Vorum 1999)and albumin binding to the gp-60 receptor (albondin) initiates the caveolae-mediated endothelial transport of protein-bound and unbound plasma constituents (John et al 2003, Minshall et al 2003, Tiruppathi et al 1997).
This study consisted of a Phase 1 dose escalation phase, a Phase 2 treatment phase and a 24-month follow-up phase.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient has histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. Patients with islet cell neoplasms are excluded.
- •Male or non-pregnant and non-lactating female, and age greater or equal to
- •If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative serum pregnancy test beta-human chorionic gonadotropin (B-hCG) documented within 72 hours of the first administration of study drug.
- •If sexually active, the patient must agree to use contraception considered adequate and appropriate by the investigator.
- •Patient must have received no prior therapy for the treatment of metastatic disease. Prior treatment with 5-fluorouracil (5-FU) or gemcitabine administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed. If a patient received gemcitabine in the adjuvant setting, tumor recurrence must have occurred at least 6 months after completing the last dose of gemcitabine.
- •Patient has the following blood counts at baseline
- •Absolute neutrophil count (ANC) equal or greater to 1.5 x 10^9/L;
- •Platelets equal or greater to 100 x 10^9/L
- •Hemoglobin equal or greater to 9 g/dL.
- •Patient has the following blood chemistry levels at baseline:
- •Aspartate aminotransferase (SGOT), Alanine aminotransferase (SGPT) equal or less than 2.5 x upper limit of normal range (ULN) is allowed
- •Bilirubin less than or equal to ULN
- •Serum creatinine within normal limits or calculated clearance equal or greater to 60 mL/min/1.73M^2 patients with serum creatinine levels above the institutional normal value
- •Patient has no clinically significant abnormalities in urinalysis results
- •Patient has acceptable coagulation status as indicated by a prothrombin time (PT) within normal limits (plus or minus 15%) and partial thromboplastin time (PTT) within normal limits (plus or minus 15%).
- •Patient has a Karnofsky performance status (KPS) greater or equal to 70 (Eastern Cooperative Oncology Group [ECOG] PS 0-1).
- •Patient has one or more metastatic tumors measurable by computed tomography (CT) scan.
- •Patient has been informed about the nature of study, and has agreed to participate in the study, and signed the Informed Consent form prior to participation in any study-related activities.
排除标准
- •Patient has known brain metastases unless previously treated and well controlled for at least 3 months (defined as stable clinically, no edema, no steroids and stable in two scans at least 4 weeks apart).
- •Patient uses therapeutic coumadin for a history of pulmonary emboli and deep vein thrombosis (DVT).
- •Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
- •Patient has known infection with human immunodeficiency virus (HIV), hepatitis B, hepatitis C.
- •Patient has undergone major surgery, other than diagnostic surgery i.e.-- done to obtain a biopsy for diagnosis without removal of an organ), with 4 weeks prior to Day 1 of treatment in this study.
- •Patient received radiotherapy, surgery, chemotherapy, or an investigational therapy within 3 weeks prior to study entry weeks (6 weeks for nitrosureas or mitomycin C).
- •Patient has a history of allergy or hypersensitivity to the study drug.
- •Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug.
- •Patient is unwilling or unable to comply with study procedures.
- •Patient is enrolled in any other clinical protocol or investigational trial.
研究组 & 干预措施
100 mg/m^2
Participants received albumin-bound paclitaxel 100 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity.
干预措施: Gemcitabine (Drug)
100 mg/m^2
Participants received albumin-bound paclitaxel 100 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity.
干预措施: Albumin-bound paclitaxel (Drug)
125 mg/m^2
Participants received albumin-bound paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity.
干预措施: Gemcitabine (Drug)
125 mg/m^2
Participants received albumin-bound paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity.
干预措施: Albumin-bound paclitaxel (Drug)
150 mg/m^2
Participants received albumin-bound paclitaxel 150 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity.
干预措施: Gemcitabine (Drug)
150 mg/m^2
Participants received albumin-bound paclitaxel 150 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity.
干预措施: Albumin-bound paclitaxel (Drug)
结局指标
主要结局
Number of Participants With Dose-limiting Toxicities
时间窗: Cycle 1 (Days 1-28)
A dose-limiting toxicity (DLT) is defined as one or more of the following toxicities related to study drug during Cycle 1, according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), Version 3: * Grade 4 neutropenia lasting \>3 days in the absence of growth factor support; * Grade 4 neutropenia associated with fever \>38.5°C; * Any other Grade 4 hematological toxicity; * Grade 3 thrombocytopenia with hemorrhage; * Grade 3 or 4 nausea, vomiting or diarrhea despite prophylaxis or treatment with an optimal anti-emetic or anti-diarrhea regimen; * Any other Grade 3 or higher non-hematological toxicity attributable to the study drug, excluding alopecia and fatigue.
次要结局
- Percentage of Participants Who Achieved an Objective Confirmed Overall Response(Up to approximately 4 years)
- Percentage of Participants With Disease Control(Up to approximately 4 years)
- Number of Participants With Adverse Events (AE)(Up to 25 months)
- Duration of Response(Up to approximately 4 years)
- Overall Survival(Up to approximately 4 years)
- Maximal Degree of Anemia(During the treatment phase, up to a maximum of 24 months.)
- Progression-free Survival(Up to approximately 4 years)
- Maximal Degree of Myelosuppression(During the treatment phase, up to a maximum of 24 months.)