NCT00097721已完成2 期
A Phase II Open Label Study of E7389 (Halichondrin B Analog) in Patients With Advanced/Metastatic Breast Cancer Previously Treated With Chemotherapy Including An Anthracycline and A Taxane
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Eisai Inc.
- 入组人数
- 104
- 主要终点
- Overall Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST)
研究概览
简要总结
The purpose of this study is to determine if E7389 is a safe and effective treatment for advanced/metastatic breast cancer.
详细描述
The primary objective is to determine the response rate (RR) to E7389 monotherapy administered as an IV bolus of 1.4 mg/m^2 on Days 1, 8, and 15 of a 28-Day cycle and on Days 1 and 8 of a 21-day cycle in patients with advanced/metastatic breast cancer treated with chemotherapy including an anthracycline and a taxane, with previously documented progression during or within six months following the last dose of prior chemotherapy.
The secondary objectives are to evaluate:
- The safety and tolerability of E7389 monotherapy in this patient population;
- The antitumor activity of E7389 as determined by duration of response, time to progression, and overall survival;
- Quality of life measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire/tumor-related symptom improvement or worsening measured by pain intensity on a visual analog scale (VAS), analgesics consumption, weight changes and performance status (PS);
- Tumor pharmacogenetics and their possible relationship to response (assessment of beta-tubulin isotype mRNA on biopsy sample) in patients who have signed a separate consent form
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Female patients with histologically or cytologically confirmed carcinoma of the breast
- •Patients with advanced/metastatic disease that is not amenable to curative therapy (either surgery or radiation therapy)
- •Patients must have measurable disease by the RECIST criteria, defined as at least one lesion that can be accurately measured in at least one diameter (at least 10 mm in longest diameter (LD) by spiral computer tomography (CT) scan, or at least 20 mm by standard techniques; If the only measurable lesion is a lymph node, it must measure at least 20 mm in LD. If a single lesion is identified as the target lesion, a cytological or histological confirmation of breast carcinoma is required.
- •Patients must have had prior treatment with an anthracycline and a taxane (either sequential or in combination) and may have had prior treatment with other agents as well.
- •Patients must have progressed within six months of the last dose of chemotherapy, or experienced disease progression while receiving chemotherapy for advanced/metastatic disease.
- •Resolution of all chemotherapy or radiation-related toxicities to less than grade 1 severity
- •Age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (APPENDIX 4) of 0 or 1
- •Life expectancy of ≥ 3 months
- •Adequate renal function as evidenced by serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 50 mL/minute (min) per the Cockcroft and Gault formula
- •Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, hemoglobin ≥ 10.0 g/dL (a hemoglobin <10.0 g/dL would be acceptable if it can be corrected by growth factor or transfusion), and platelet count ≥ 100 x 10^9/L
- •Adequate liver function as evidenced by bilirubin ≤ 1.5 mg/dL and alkaline phosphatase, alanine transaminase (ALT), and aspartate transaminase (AST) ≤ 3 times the upper limits of normal (ULN) (in the case of liver metastases ≤ 5 x ULN)
- •Patients willing and able to complete the FACT-B questionnaire, Analgesic Diary, Pain VAS, and the tumor-related symptomatic assessment
- •Patients willing and able to comply with the study protocol for the duration of the study
- •A sample from the diagnostic biopsy (paraffin block) must be available
- •Written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice
排除标准
- •Patients who have received chemotherapy, radiation, hormonal therapy, or Herceptin within 2 weeks of E7389 treatment start
- •Radiation therapy encompassing > 10% of marrow
- •Failure to recover from any chemotherapy related or other therapy related toxicity at study entry that is deemed to be clinically significant by the study investigator
- •Prior treatment with Mitomycin C or nitrosoureas
- •Prior high dose chemotherapy with hematopoietic stem cell rescue in the past two years
- •Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
- •Active symptomatic brain metastasis; Patients with central Nervous System (CNS) metastasis are considered eligible if they have completed local therapy and discontinued from corticosteroids for at least two weeks before starting treatment with E7389
- •Patients with meningeal carcinomatosis
- •Patients who require therapeutic anti-coagulant therapy with Warfarin or related compounds; Mini dose warfarin for catheter related thrombosis prophylaxis is permitted
- •Women who are pregnant or breast-feeding; Women of childbearing potential with either a positive pregnancy test at Screening or no pregnancy test. Women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the Investigator. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
- •Severe /uncontrolled intercurrent illness/infection
- •Significant cardiovascular impairment (history of congestive heart failure > NYHA grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia)
- •Patients with organ allografts
- •Patients with known positive HIV status
- •Patients who have had a prior malignancy, other than carcinoma in situ of the cervix, or non-melanoma skin cancer, unless the prior malignancy was diagnosed and definitively treated ≥ 5 years previously with no subsequent evidence of recurrence
- •Patients with pre-existing neuropathy > Grade 1
- •Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative
- •Patients who participated in a prior E7389 clinical trial
- •Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study
研究组 & 干预措施
E7389
Experimental
干预措施: E7389 (Drug)
结局指标
主要结局
Overall Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST)
时间窗: Confirmed 4 to 8 weeks after first observed
Defined as the percentage of subjects with CR or PR from the start of treatment until disease progression or recurrence. Lesions measured by computed tomography (CT) scan and magnetic resonance imaging (MRI). Objective response rate: complete response (CR-disappearance of all lesions)+ partial response (PR-30% decrease in lesion diameter), Progressive Disease (PD-20% increase in lesion diameter), stable disease (SD-neither shrinkage nor increase of lesions).
次要结局
- Duration of Response(From CR or partial response PR (whichever recorded first) to date of recurrent or progressive disease)
- Progression Free Survival(From start of study drug administration to progressive disease or death)
- Overall Survival(From start of study drug administration to death)
- Change From Baseline to Study Termination in Quality of Life Measures Using Functional Assessment of Cancer Therapy-Breast (FACT-B) Scores(At Screening, Day 1 of each cycle, and 30 days after last dose of study drug)
研究者
相似试验
已完成
2 期
E7389 in Treating Patients With Recurrent or Progressive Stage IIIB or Stage IV Non-Small Cell Lung CancerRecurrent Non-small Cell Lung CancerStage IIIB Non-small Cell Lung CancerStage IV Non-small Cell Lung CancerNCT00400829National Cancer Institute (NCI)66
已完成
2 期
Eribulin Mesylate as Second-Line Therapy for Locally Advanced, Unresectable, or Metastatic Pancreatic Cancer PatientsAdenocarcinoma of the PancreasRecurrent Pancreatic CancerStage II Pancreatic CancerStage III Pancreatic CancerStage IV Pancreatic CancerPancreatic CancerNCT00383760National Cancer Institute (NCI)15
已完成
1 期
E7389 in Treating Patients With Advanced Solid TumorsUnspecified Adult Solid Tumor, Protocol SpecificNCT00047034National Cancer Institute (NCI)31
已完成
2 期
A Phase II Study of E7389 in Patients With Breast Cancer, Previously Treated With Anthracycline, Taxane and CapecitabineBreast CancerNCT00246090Eisai Inc.298
已完成
2 期
E7389 Administered as an IV Bolus Infusion Day 1 and Day 8 Every 3 Weeks in Pre-Treated Patients With Advanced and/or Metastatic Soft Tissue SarcomaSoft Tissue SarcomaNCT00413192Eisai Inc.128