A Phase II Study of Eribulin (NSC# 707389) in Recurrent or Refractory Osteosarcoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 119
- 主要终点
- Response Evaluation Criteria in Solid Tumors (RECIST) Response
研究概览
简要总结
This phase II trial studies how well eribulin mesylate works in treating patients with osteosarcoma that has come back after treatment (recurrent) or has not responded to treatment (refractory). Microtubule inhibitors, such as eribulin mesylate, may stop or slow the growth of tumor cells by disrupting the cell cycle.
详细描述
PRIMARY OBJECTIVES:
I. To estimate the 4 month progression free survival rate and objective response rate in patients with recurrent osteosarcoma who are administered eribulin (eribulin mesylate) therapy on day 1 and day 8 of 21 day cycles.
SECONDARY OBJECTIVES:
I. To investigate the pharmacokinetics (PK) of eribulin in subjects with recurrent osteosarcoma.
II. To further describe the tolerability of single agent eribulin.
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
- 12 Years 至 49 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have had histologic verification of osteosarcoma at original diagnosis
- •Patients must have measurable disease, documented by clinical, radiographic, or histologic criteria, and have relapsed or become refractory to conventional therapy
- •Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
- •Patients must have a life expectancy of >= 8 weeks
- •Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- •Myelosuppressive chemotherapy: must not have received within 2 weeks of entry onto this study (6 weeks if prior nitrosourea)
- •Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent
- •Bisphosphonates: at least 4 weeks since the completion of therapy with a bisphosphonate
- •Monoclonal antibodies: at least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
- •Radiation therapy (RT): >= 2 weeks (wks) for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation
- •Peripheral absolute neutrophil count (ANC) >= 1000/uL
- •Platelet count >= 75,000/uL (transfusion independent)
- •Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)
- •Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or
- •A serum creatinine based on age/gender as follows: (threshold creatinine values were derived from the Schwartz formula for estimating GFR)
- •Age (12 to < 13 years) - serum creatinine of 1.2 mg/dL
- •Age (13 to < 16 years) - serum creatinine of 1.5 mg/dL (male) and 1.4 mg/dL (female)
- •Age (>= 16 years) - serum creatinine of 1.7 mg/dL (male) and 1.4 mg/dL (female)
- •Bilirubin (sum of conjugate + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
- •Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 units per liter (U/L); for the purpose of this study, the ULN for SGPT is 45 U/L
- •Serum albumin > 2 g/dL
- •Shortening fraction of >= 27% by echocardiogram
- •Ejection fraction of >= 50% by radionuclide angiogram
- •All patients and/or their parents or legal guardians must sign a written informed consent
- •All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
排除标准
- •Patients with congenital prolonged QT syndrome
- •Patients with a baseline QT/corrected QT (QTc) interval >= 501 msec
- •Patients who are receiving drugs that prolong the QTc are not eligible
- •Patients who have previously received eribulin, halichondrin B, or analogues of halichondrin B
- •Patients who have grade >= 2 peripheral neuropathy
- •Patients who are receiving other cancer directed therapy at the time of enrollment
- •Patients who have had major surgery within 3 weeks prior to enrollment are not eligible; procedures such as placement of a central vascular catheter, or limited tumor biopsy, are not considered major surgery
- •Pregnancy and breast feeding
- •Female patients who are pregnant are ineligible
- •Lactating females are not eligible unless they have agreed not to breastfeed their infants
- •Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
- •Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
研究组 & 干预措施
Treatment (eribulin mesylate)
Patients receive eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
Treatment (eribulin mesylate)
Patients receive eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
干预措施: Eribulin Mesylate (Drug)
结局指标
主要结局
Response Evaluation Criteria in Solid Tumors (RECIST) Response
时间窗: 4 months
The number of patients who experience a complete or partial response according to the RECIST criteria as defined in Eisenhauer et al. Eur J Cancer 45:228-47, 2009.
Disease Control Success
时间窗: 4 Months
The number of patients who do not experience disease progression or death in the four months following enrollment on AOST1322.
次要结局
- Number of Cycles Where a Dose Limiting Toxicity Was Identified(4 months)
- Area Under the Curve 0-infinity of Eribulin Mesylate in Ng-hr/ml(Cycle 1 day 1 and cycle 2 day 1 at the end of infusion, 0.5-6 hours, and 24-120 hours post infusion; cycle 1 day 8 and cycle 2 day 8 prior to the dose of eribulin and at the end of infusion)
- Clearance of Eribulin Mesylate in L/hr(Cycle 1 day 1 and cycle 2 day 1 at the end of infusion, 0.5-6 hours, and 24-120 hours post infusion; cycle 1 day 8 and cycle 2 day 8 prior to the dose of eribulin and at the end of infusion.)
- A Half Life of Eribulin Mesylate in hr(1 day 1 and cycle 2 day 1 at the end of infusion, 0.5-6 hours, and 24-120 hours post infusion; cycle 1 day 8 and cycle 2 day 8 prior to the dose of eribulin and at the end of infusion)