A Phase II Trial Assessing the Tolerability of Palbociclib in Combination With Letrozole or Fulvestrant in Patients Aged 70 and Older With Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 入组人数
- 93
- 试验地点
- 446
- 主要终点
- Incidence of Adverse Events
研究概览
简要总结
This phase II trial studies the side effects and how well palbociclib and letrozole or fulvestrant works in treating patients aged 70 years and older with estrogen receptor positive, HER2 negative breast cancer that has spread to other places in the body. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as letrozole or fulvestrant, 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. Giving palbociclib and letrozole or fulvestrant may work better in treating patients with breast cancer. The trial will explore factors other than chronologic age that can affect toxicity rates as identified using a cancer-specific geriatric assessment.
详细描述
PRIMARY OBJECTIVES:
I. To estimate the safety and tolerability (adverse event rate) of the combination of palbociclib and letrozole or fulvestrant in adults age 70 or older with estrogen receptor-positive, HER2-negative metastatic breast cancer.
SECONDARY OBJECTIVES:
I. To describe the full toxicity profile including all grade 2 and higher adverse events (per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v.] 5.0), specifically estimating the rate of grade 2 and higher myelosuppression (neutropenia, leukopenia, thrombocytopenia, and anemia), neutropenic fever, gastrointestinal (GI) side effects (nausea, diarrhea, decreased appetite, vomiting, mucositis-oral), fatigue, neuropathy, and thromboembolism.
II. To describe rates of dose reductions, dose holds, and hospitalizations. III. To estimate median time to treatment failure, including progression free survival and overall survival.
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
- 70 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documentation of disease: estrogen receptor positive and/or progesterone receptor (PR) positive, HER2 negative metastatic breast cancer; histologic confirmation is required
- •Measurable disease or non-measurable disease
- •Planning to begin palbociclib for metastatic disease; one prior line of endocrine therapy and/or chemotherapy for metastatic disease is allowed; patients may begin or have already begun endocrine therapy before they start palbociclib treatment, but no more than two weeks prior to registration
- •No prior therapy with a CDK inhibitor
- •Resolution of all acute toxic effects of prior therapy or surgical procedures to CTCAE grade =< 1 (except alopecia) or to baseline toxicities prior to previous therapy or surgical procedures, prior to registration
- •No untreated brain metastases; patients with treated brain metastases must have completed treatment with steroids to be eligible
- •No known interstitial lung disease
- •No second malignancies other than non-melanoma skin cancers or cervical carcinoma in situ; however, patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for >= 3 years
- •No active infection requiring treatment with antibiotics
- •Patients must be able to swallow and retain oral medication
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
- •Patients must be able to read and comprehend English or Spanish
- •Absolute neutrophil count (ANC) >= 1500/mm^3 (1.5 x 10^9/L)
- •Platelet count >= 100,000/mm^3 (100 x 10^9/L)
- •Creatinine clearance >= 30 ml/min calculated using the Cockcroft-Gault formula
- •Total serum bilirubin =< 1.5 upper limit of normal (ULN) (< 3 ULN if Gilbert's disease)
- •Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x ULN (=< 5.0 x ULN if liver metastases present)
- •Alkaline phosphatase =< 2.5 x ULN (=< 5 x ULN if bone or liver metastases present)
排除标准
- 未提供
研究组 & 干预措施
Treatment (palbociclib, letrozole or fulvestrant)
Patients receive palbociclib PO QD on days 1-21. Patients also receive letrozole PO QD on days 1-28 or fulvestrant IM on days 1 and 15 of course 1 and on day 1 of subsequent courses per MD discretion. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Palbociclib (Drug)
Treatment (palbociclib, letrozole or fulvestrant)
Patients receive palbociclib PO QD on days 1-21. Patients also receive letrozole PO QD on days 1-28 or fulvestrant IM on days 1 and 15 of course 1 and on day 1 of subsequent courses per MD discretion. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Letrozole (Drug)
Treatment (palbociclib, letrozole or fulvestrant)
Patients receive palbociclib PO QD on days 1-21. Patients also receive letrozole PO QD on days 1-28 or fulvestrant IM on days 1 and 15 of course 1 and on day 1 of subsequent courses per MD discretion. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Fulvestrant (Drug)
Treatment (palbociclib, letrozole or fulvestrant)
Patients receive palbociclib PO QD on days 1-21. Patients also receive letrozole PO QD on days 1-28 or fulvestrant IM on days 1 and 15 of course 1 and on day 1 of subsequent courses per MD discretion. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Treatment (palbociclib, letrozole or fulvestrant)
Patients receive palbociclib PO QD on days 1-21. Patients also receive letrozole PO QD on days 1-28 or fulvestrant IM on days 1 and 15 of course 1 and on day 1 of subsequent courses per MD discretion. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
结局指标
主要结局
Incidence of Adverse Events
时间窗: 6 months
Defined as the proportion of patients with documentation of grade 3 - 5 toxicity (regardless of attribution using the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v.\] 5.0 criteria). A 95% binomial confidence interval for single proportions will be constructed for the severe toxicity rate during treatment. Univariate relationships between the primary endpoint and various pre-treatment patient characteristics such as anemia, self-assessed functional status, or social support will be described via cross-tabulation and Fisher's exact testing. Exploratory logistic regression modeling, with limited generalizability due to the modest sample size, will be used to assess the relative contributions of these variables impact the likelihood of developing a severe toxicity during treatment. The strength of this association will be expressed in terms of an odds ratio and its associated 95% confidence interval.
次要结局
- Incidence of Drug Toxicities - Measured by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v. 5.0(Up to 1 year)
- Dose Reduction, Dose Hold, and Hospitalization Reasons(Up to 1 year)
- Time to Treatment Failure (and Reason for Coming Off Study - Toxicity, Patient Preference, Progression)(Up to 5 years)
- Palbociclib Adherence Rate(Up to 12 weeks)
- Response Rate as Determined by Response Evaluation Criteria in Solid Tumors (RECIST)(Up to 1 year)
- Progression Free Survival (PFS)(From start of treatment to the first of the following disease events: local/regional/distant recurrence, invasive contralateral breast disease, second primary or death due to any cause, assessed up to 5 years)
- Overall Survival (OS)(Up to 5 years)
- Overall Treatment Utility (OTU) Results(Up to 1 year)
- Sarcopenia Analysis(Up to 1 year)
- Quality of Life as Measured by the European Quality of Life Five Dimension Three Level Questionnaire (EQ-5D-3L)(Up to 1 year)