Dose Reduction of Docetaxel-Based Chemotherapy in Vulnerable Older Women With Early-Stage Breast Cancer (DOROTHY)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 174
- 试验地点
- 4
- 主要终点
- Relative dose intensity (RDI)
研究概览
简要总结
This phase II trial tests how well dose-reduced docetaxel combined with cyclophosphamide works in treating older women with early stage (stage I-III) HER2 negative breast cancer vulnerable to toxicity. Chemotherapy drugs, such as docetaxel and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Docetaxel and cyclophosphamide are commonly used, but is not well tolerated at the standard dose and can affect the way older patients feel physically and emotionally. Giving dose-reduced docetaxel combined with cyclophosphamide may be an effective treatment option and improve quality of life in vulnerable older women with stage I-III HER2 negative breast cancer.
详细描述
PRIMARY OBJECTIVE:
I. Compare the relative dose intensity (RDI) of reduced- versus (vs.) standard-dose docetaxel dosing strategies.
SECONDARY OBJECTIVE:
I. Compare treatment tolerability of reduced- vs. standard-dose docetaxel dosing strategies.
OUTLINE: Patients are randomized to 1 of 2 arms.
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 (Investigator)
盲法说明
Randomization module also conceals allocation from other study personnel except the biostatistician and the designated study coordinator by limiting their user's right.
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to provided informed consent or a legally authorized representative is able to consent on behalf of the patient
- •Willing to answer questionnaires as part of their participation
- •Age: >= 65 years by the time of study registration
- •Histologically or cytologically confirmed breast cancer(s) that is human epidermal growth factor receptor 2 negative (HER2-negative) per the most recent 2018 American Society of Clinical Oncology College of American Pathologists (ASCO CAP) guidelines relapsed/ refractory disease
- •Estrogen receptor and progesterone receptor immunohistochemistry (IHC) status must be known; any estrogen receptor (ER)/progesterone receptor (PR) status is eligible
- •Non-metastatic, invasive breast cancer (scans are not required to document non-metastatic disease- any staging work-up is up to the treating providers' discretion)
- •Recommended to have either standard dose neoadjuvant docetaxel, cyclophosphamide (TC) chemotherapy or adjuvant TC chemotherapy per their treating provider. Participant may be on immunotherapy concurrently with the protocol regimen at the discretion of the treating physician
- •Any surgery, nodal assessment, radiation, hormonal therapy is left up to the treating provider but should not occur concurrently with study therapy
- •Any patient who received pre-operative hormonal therapy and who is then recommended for neo/adjuvant chemotherapy is eligible, though hormonal therapy should be held during study treatment administration
- •For patients with bilateral or multifocal/multicentric breast cancers, the following criteria must be met to enroll: (1) both cancer are HER2 negative, AND (2) the provider feels the patient will benefit from TC for at least one of the cancers
- •Patients who do not speak or read English are eligible as long as adequate interpreter services are available or the surveys are available in the preferred language (i.e. the Geriatric Assessment [GA] and Patient Reported Outcomes [PRO] surveys are available in many languages)
排除标准
- •Participants who have already received any chemotherapy for their current breast cancer
- •Patients with recurrent and/or metastatic disease will be excluded. Prior diagnoses of breast cancers (including ductal carcinoma in situ [DCIS]) are allowed, provided that the treating provider feels that the current cancer most likely represents a new primary breast cancer and not recurrent disease
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide and/or docetaxel
- •Past treatment with the regimen TC for prior breast cancer
研究组 & 干预措施
Arm I: (Dose-reduced docetaxel, cyclophosphamide)
Patients receive dose-reduced docetaxel IV over 60 minutes and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Medical Chart Review (Other)
Arm I: (Dose-reduced docetaxel, cyclophosphamide)
Patients receive dose-reduced docetaxel IV over 60 minutes and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Arm II: (Standard dose docetaxel, cyclophosphamide)
Patients receive standard dose docetaxel IV over 60 minutes and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Medical Chart Review (Other)
Arm II: (Standard dose docetaxel, cyclophosphamide)
Patients receive standard dose docetaxel IV over 60 minutes and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Arm I: (Dose-reduced docetaxel, cyclophosphamide)
Patients receive dose-reduced docetaxel IV over 60 minutes and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Docetaxel (Drug)
Arm I: (Dose-reduced docetaxel, cyclophosphamide)
Patients receive dose-reduced docetaxel IV over 60 minutes and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Cyclophosphamide (Drug)
Arm II: (Standard dose docetaxel, cyclophosphamide)
Patients receive standard dose docetaxel IV over 60 minutes and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Cyclophosphamide (Drug)
Arm II: (Standard dose docetaxel, cyclophosphamide)
Patients receive standard dose docetaxel IV over 60 minutes and cyclophosphamide IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Relative dose intensity (RDI)
时间窗: At completion of 4 cycles, up to 12 weeks (each cycle is every three weeks)
RDI is defined as the ratio of actual dose intensity received to the standard dose intensity, ranging from 0 to 100%. The RDI between the two arms will be compared using T-test, RDI difference and 90% confidence interval. A one-sided p-value \< 0.05 will be considered statistically significant.
次要结局
- Changes in function and health status(At baseline and at 3, 6, 12 and 24 months after treatment ends)
- Incidence of adverse events(At every 3 weeks up to completion of study treatment)
- Overall survival(From registration to death due to any cause up to 24 months)
- Treatment success(At completion of 4 cycles, up to 12 weeks (Each cycle is three weeks))
- Patient-reported symptomatic toxicities(At each chemotherapy cycle for 4 cycles, end of treatment and at 3, 6, 12 and 24 months after treatment ends)(Each cycle is three weeks).)
- Progression-free survival(From registration to the earliest of progression or death due to any cause up to 24 months)
- Differences in PRO-CTCAE and clinician-reported toxicities(At each chemotherapy cycle for 4 cycles and at 3, 6, 12, and 24 months after treatment ends (Each cycle is three weeks).)
- Patient satisfaction(Up to 3 months after treatment ends)
- Invasive disease-free survival(Up to 2 years)
- Local recurrences(Up to 3 years)
- Distant recurrences(Up to 2 years)