A Phase II, Multicenter, Randomized Trial of Eribulin Plus Gemcitabine (EG) vs.Paclitaxel Plus Gemcitabine (PG) in Patients With HER2-Negative Metastatic Breast Cancer as First -Line Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 118
- 试验地点
- 2
- 主要终点
- Progression free survival
研究概览
简要总结
Metastatic breast cancer (MBC) is an incurable disease and is needed to improve effective chemotherapy. Paclitaxel plus Gemcitabine (PG) combination chemotherapy is one of the preferred chemotherapeutic regimens for patients with MBC, and was found to be proper as a maintenance chemotherapy regimen with survival benefit and feasible toxicity profile as shown in a large phase III KCSG (Korean Cancer Study Group) study (Park Y et al. J Clin Oncol 31(14):1732, 2013).
Eribulin mesylate is a microtubule-targeting agent that showed improved overall survival benefit as monotherapy for MBC patients as a new chemotherapeutic agent after failure of anthracycline and taxane in EMBRACE study (Cortes J et. al. Lancet 377:914-923, 2011). Eribulin was also reported its promising efficacy in another randomized phase III study that demonstrated eribulin as efficacious as capecitabine (Kaufman P et. al. Abstr# S6-6, SABCS 2012). Both study results showed potential clinical benefit in patients with triple negative MBC (TNBC). Thus, eribulin combined with gemcitabine may be a new potential regimen for early line therapy in patients with metastatic breast cancer.
Furthermore, eribulin may have rational benefit compared with paclitaxel in terms of neurotoxicity. Although there is no direct evidence that eribulin has better neurotoxicity profile than taxane, eribulin tended to show less neurotoxicity compared with ixabepilone in a phase II trial (Vahdat, L et al. 2011 SABCS). Eribulin has no worsen toxicity as compared to paclitaxel. Therefore, EG may have less neurotoxicity comparing to PG.
In phase I trial, eribulin in combination with gemcitabine was feasible in patients with advanced solid tumor treated with chemotherapy (< 3 lines) (Goel R, et al, 2009 ASCO).
Based on this rationale, the investigators are to conduct randomized phase II study comparing EG chemotherapy with PG chemotherapy for patients with HER-2 negative MBC as first-line chemotherapy.
A total of 118 patients will be recruited. Patients will be randomized to a treatment arm by permutated method. The randomization ratio is 1:1. This study is multi-center, randomized, open label study.
详细描述
A total of enrolled 118 patients in EG and PG groups, will be provided chemotherapy regimen:
Paclitaxel/Gemcitabine (PG) : every 3 weeks D1 Paclitaxel 175mg/m2 + D5W 500mL MIV over 3hrs before gemcitabine administration D1, D8 Gemcitabine 1,250 mg/m2 + NormalSaline 100ml MIV over 30mins
- Pre & Post medication (which can be changed according to institutions' policy) D1 Corticosteroid 100 mg i.v. 30 min. before Paclitaxel Pheniramine 1A + D5W 50mL MIV 30mins before Paclitaxel Ranitidine 50mg IV + D5W 50mL MIV 30mins before Paclitaxel HT3 antagonist 1A + D5W 50 mL MIV 30mins before Paclitaxel
Eribulin/Gemcitabine (EG): every 3weeks D1, D8 Eribulin 1.0 mg/m2, 2-5min iv before gemcitabine (or miv with NormalSaline 100ml in max.) D1, D8 Gemcitabine 1000 mg/m2 + NormalSaline100ml MIV over 30mins
<schedule of Assessment adn procedures (±3 days window period ) >
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed metastatic, or recurrent breast cancer
- •HER2-negative breast cancer
- •age > 18 years
- •ECOG performance status 0 - 2
- •Pre- or postmenopausal breast cancer patients with measurable or non-measurable lesions, who are candidates for chemotherapy
- •Life expectancy ≥ 3 months
- •No prior history of chemotherapy for metastatic, recurrent breast cancer
- •Patients may have received prior neoadjuvant or adjuvant taxane regimen as long as it has been 12 months since completion of regimen.
- •Patients either may or may not have a prior anthracycline containing regimen.
- •Prior hormonal therapy as a treatment of metastatic disease is allowed. But antitumoral hormonal therapy must be terminated prior to enrollment(up to the date of randomization)
- •Prior radiation therapy allowed as long as < 25% of the bone marrow has been treated, and the patients must have recovered from the acute toxic effects of the treatment prior to study enrollment. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed 2 weeks before study entry.
- •Bisphosphonates for the treatment of bone metastases should not be initiated following the first dose of randomized therapy. It must be initiated prior to day of treatment (cycle 1, day 1). Patients may continue on bisphosphonates who already established on bisphosphonate therapy for bone metastases
- •Adequate bone marrow function (≥ ANC 1,500/ul, ≥ platelet 100,000/ul, ≥ Hemoglobin 9.0 g/dl)
- •Adequate renal function (≤ serum creatinine 1.5 mg/dl or CCr ≥ 50 ml/min)
- •Adequate liver function (≤ serum bilirubin 1.5 mg/dl, ≤ AST & ALTX3 upper normal limit or AST and ALT ≤ 5.0XULN if judged by the investigator to be related to liver metastases)
- •Written informed consent
排除标准
- •Serious uncontrolled intercurrent infections
- •Serious intercurrent medical or psychiatric illness, including active cardiac disease
- •Pregnancy or breast feeding
- •Second primary malignancy(except in situ carcinoma of the cervix or adequately treated nonmelanomatous carcinoma of the skin or other malignancy treated at least 5 years previously with no evidence of recurrence)
- •Documented parenchymal or leptomeningeal brain metastasis
- •Peripheral neuropathy ≥ grade 2
- •Prior treatment with gemcitabine will not be allowed.
- •HER-2 overexpressing breast cancer and concomitant trastuzumab treatment is not allowed
- •Women of childbearing potential, unwilling to use a medically acceptable method of contraception during the trial
研究组 & 干预措施
Paclitaxel & Gemcitabine(PG)
Paclitaxel 175mg/m2 IV , Day1,every 3weeks Gemcitabine 1250mg/m2 IV ,Day1& Day8 every 3weeks
干预措施: Paclitaxel (Drug)
Paclitaxel & Gemcitabine(PG)
Paclitaxel 175mg/m2 IV , Day1,every 3weeks Gemcitabine 1250mg/m2 IV ,Day1& Day8 every 3weeks
干预措施: Gemcitabine (Drug)
Eribulin & Gemcitabine(EG)
Eribulin 1.0 mg/m2, 2-5min iv ,Day1& Day8 every 3weeks Gemcitabine 1,000 mg/m2 ,Day1& Day8 every 3weeks
干预措施: Eribulin (Drug)
Eribulin & Gemcitabine(EG)
Eribulin 1.0 mg/m2, 2-5min iv ,Day1& Day8 every 3weeks Gemcitabine 1,000 mg/m2 ,Day1& Day8 every 3weeks
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Progression free survival
时间窗: 48months
To demonstrate that EG is not inferior to PG group in terms of PFS in patients with metastatic or recurrent breast cancer as first-line treatment.
次要结局
- duration of response(48months)
- overall survival(48months)
- neuropathic scale(expected at 9week , expected at 24week)
- toxicity of study drugs(from first administration until 28 days after the last dose administration)
- objective response rate(48months)
- clinical benefit rate(48months)
研究者
Kyung Hae Jung
Professor
Asan Medical Center