A Phase 2 Study of Eribulin in Patients With HER2-Negative, Metastatic Breast Cancer: Evaluation of Efficacy, Toxicity and Patient-Reported Outcomes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 83
- 试验地点
- 7
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
Improvements in outcomes with metastatic breast cancer (MBC) have been observed in the last 30 years, however, overall prognosis remains poor with median survival of 2 to 3 years. Long term complete responses are observed only for a minority of MBC patients (2-5%) and MBC remains an incurable disease for most patients. Eribulin is a chemotherapy approved by the US FDA in November of 2010 to treat patients with MBC who have received at least two prior chemotherapy regimens. In this research study, the investigators are looking to see how well eribulin helps participants with MBC in an earlier-line setting. Eribulin works by interfering with cancer cell division, growth and spread.
详细描述
Based on positive results in heavily pre-treated MBC patients, eribulin is being studied as first-line or second-line chemotherapy treatment. This is a non-randomized, open label study with participants enrolled in one of two cohorts: Cohort 1. Hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) or Cohort 2: Triple negative breast cancer (TNBC) meaning HR-negative/HER2-negative (HR-/HER2-). HR- means progesterone receptor-negative (PR-) and estrogen receptor-negative (ER-). Beyond efficacy as measured primarily by response to treatment, investigators will evaluate safety, tolerability and quality of life. In particular, it is hypothesized that eribulin may have lower rates of neuropathy, a common side effect of many of the major chemotherapeutics with activity in MBC. The investigators will study the effect eribulin has on the nerves through regular questionnaires that ask about any nerve-related symptoms. The investigators also plan to send blood samples to explore if gene markers may indicate increased sensitivity to the nerve effects of eribulin.
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
- •Histologically or cytologically proven invasive breast cancer, locally recurrent or metastatic, with at least one measureable lesion according to RECIST v1.1
- •Hormone receptor positive or hormone receptor negative HER2-negative disease
- •Up to one prior line of chemotherapy for advanced disease is allowed (discontinued at least 14 days prior to initiation of protocol therapy)
- •Prior bevacizumab in the neo/adjuvant or metastatic setting is acceptable
- •No limit on prior lines of endocrine therapy, but must be discontinued at least 7 days prior to initiation of protocol therapy
- •Must have completed any prior radiotherapy at least 2 weeks prior to initiation of protocol therapy
- •Must have recovered from reversible effects of prior therapies to no more than grade 1 toxicity, with the exception of alopecia
- •Agree to use adequate contraception for the duration of study participation
排除标准
- •Pregnant or breastfeeding
- •Prior treatment with eribulin
- •Prior malignancy other than carcinoma in situ of the cervix or nonmelanoma skin cancer unless diagnosed and definitively treated at least 3 years before enrollment in this study
- •Clinically significant cardiovascular impairment
- •Active brain metastases or unevaluated neurologic symptoms suggestive of brain metastases
- •Pulmonary dysfunction requiring the use of oxygen
- •Prior organ allograft requiring immunosuppression
- •HIV positive on combination antiretroviral therapy
- •Pre-existing grade 3 or 4 neuropathy
- •Hypersensitivity to halichondrin B or halichondrin B chemical derivative
- •Uncontrolled intercurrent illness
- •Inability to read in English
研究组 & 干预措施
Cohort 1: HR+/HER2-
Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle
Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.
干预措施: Eribulin (Drug)
Cohort 2: TNBC
Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle
Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.
干预措施: Eribulin (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Disease was evaluated radiologically at baseline and every 9 weeks on treatment; Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2)
ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
次要结局
- Percentage of Participants With Grade 1-3 Treatment-Related Peripheral Sensory Neuropathy(Adverse events were assessed every cycle throughout treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2))
- Progression-Free Survival (PFS)(Disease was evaluated radiologically at baseline and every 9 weeks on and off treatment; Median (maximum) PFS follow-up was 12.6 (27.1) months in Cohort 1 and 12.4 (14.3) months in Cohort 2.)
- Time to First Response (TTR)(Disease was evaluated radiologically at baseline and every 9 weeks on treatment; Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2).)
- Duration of Overall Response (DOR)(Disease was evaluated radiologically at baseline and every 9 weeks on and off treatment; Median (maximum) DOR follow-up was 12.6 (27.1) months in Cohort 1 and 12.4 (14.3) months in Cohort 2.)
- Percentage of Participants With Grade 1-3 Treatment-Related Peripheral Motor Neuropathy(Adverse events were assessed every cycle throughout treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2))
- Functional Assessment of Cancer Therapy-Breast Cancer Subscale (FACT-BCS) Change Score From Baseline(Assessed at baseline and on treatment day 1 of cycles 2, 3, 5, 7, 9 and 11)
- Functional Assessment of Cancer Therapy-Neurotoxicity Subscale (FACT-Ntx) Change Score From Baseline(Assessed at baseline and on treatment day 1 of cycles 2, 3, 5, 7, 9 and 11)
研究者
Erica Mayer, MD, MPH
Principal Investigator
Dana-Farber Cancer Institute