Single Arm Pilot Trial of Adaptive Therapy (AT) With Capecitabine for the Treatment of Metastatic Estrogen Receptor Positive, Hormone Refractory Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Mayo Clinic
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- Ability to achieve adaptive therapy (AT)
研究概览
简要总结
This phase II trial evaluates the effect of capecitabine on tumor response using imaging and tumor markers to adjust dose (adaptive therapy) in patients with estrogen receptor (ER) positive, HER2 negative breast cancer that has spread from where it first started to other areas in the body (metastatic). Capecitabine is in a class of medications called antimetabolites. It is taken up by tumor cells and breaks down into fluorouracil, a substance that kills tumor cells. Adaptive therapy with capecitabine based on tumor burden response may slow or stop the growth of tumor cells in patients with metastatic ER positive, HER2 negative breast cancer.
详细描述
PRIMARY OBJECTIVE:
I. Evaluate the feasibility of adaptive therapy (AT) in hormone receptor positive metastatic breast cancer, defined as the number of patients who can achieve AT modification for 2 or more cycles.
SECONDARY OBJECTIVES:
I. To evaluate time to progression in patients receiving capecitabine AT defined as the interval between treatment start and tumor progression, or death in patients with no evidence of disease progression.
II. Assess overall survival in patients receiving capecitabine as adaptive therapy.
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
- All
- 接受健康志愿者
- 否
入选标准
- •PRE-REGISTRATION: Provide written informed consent Note: Pre-registration should occur prior to screening research blood draws being completed
- •PRE-REGISTRATION: Provider anticipates the patient will begin on capecitabine within 14 days or has started capecitabine within the past 42 days and has had a maximum of two cycles Note: Pre-registration should occur prior to screening research blood draws being completed
- •REGISTRATION - INCLUSION CRITERIA
- •Age ≥ 18 years
- •Histological confirmation of estrogen-receptor positive (ER+), HER2-negative overexpression or amplification negative as per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines, metastatic breast cancer
- •Measurable disease. Bone only disease allowed if associated with soft tissue component that is measurable by Response Evaluation Criteria is Solid Tumors (RECIST) 1.1 criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- •Hemoglobin ≥ 9.0 g/dL (obtained ≤ 14 days prior to registration), no transfusions allowed ≤ 14 days prior to registration
- •Absolute neutrophil count (ANC) ≥ 1500/mm^3 (obtained ≤ 14 days prior to registration)
- •Platelet count ≥ 100,000/mm^3 (obtained ≤ 14 days prior to registration)
- •Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 14 days prior to registration)
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 14 days prior to registration)
- •Calculated creatinine clearance ≥ 30 ml/min using the Cockcroft-Gault formula (obtained ≤ 14 days prior to registration)
- •Negative serum or urine pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only. NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- •Provide written informed consent
- •Ability to complete questionnaire(s) by themselves or with assistance
- •Willingness to provide mandatory blood specimens for correlative research
- •Ability to undergo re-staging CT scans as required by the protocol
- •Note: for patients who have had up to two cycles of capecitabine prior to joining the study, they must have had their initial CT imaging completed within 28 days of their first dose of capecitabine
- •Willing to return to enrolling institution at the specified frequency for follow-up (during the active monitoring phase of the study)
- •Cohort 2 only: Stable disease, partial or complete response on imaging after beginning capecitabine
排除标准
- •Prior chemotherapy or use of antibody drug conjugate in the metastatic setting
- •Note - Cohort 2 only: Patients can have had up to two cycles of capecitabine before joining the study
- •Any of the following, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
- •Pregnant persons
- •Nursing persons
- •Persons of childbearing potential who are unwilling to employ adequate contraception
- •Any of the following prior therapies:
- •Major surgery ≤ 3 weeks prior to registration
- •Radiation therapy ≤ 2 weeks prior to registration
- •Evidence of visceral crisis or impending cord compression
- •Evidence of uncontrolled brain metastasis requiring whole brain irradiation or intervention
- •Uncontrolled intercurrent illness including, but not limited to:
- •ongoing or active infection
- •symptomatic congestive heart failure
- •unstable angina pectoris
- •uncontrolled cardiac arrhythmia
- •chronic oxygen dependence
- •respiratory failure
- •or psychiatric illness/social situations that would limit compliance with study requirements
- •Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
- •Other active malignancy ≤ 3 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
- •If there is a history of prior malignancy, they must not be receiving other cancer specific treatment. Except for antiestrogen treatment (aromatase inhibitors or selective estrogen modulators) for their cancer are permitted if they meet other eligibility criteria. Denosumab and zoledronic acid, are permitted as established adjunct therapies per guidelines
- •History of myocardial infarction ≤ 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- •Patients known to have certain homozygous or compound heterozygous dihydropyrimidine dehydrogenase (DPYD) variants that result in complete absence of deoxypyridinoline (DPD) activity. Test results do not need to be available prior to registration
- •History of severe hypersensitivity reactions to fluorouracil or capecitabine
研究组 & 干预措施
Treatment (capecitabine)
See Detailed Description.
干预措施: Biospecimen Collection (Procedure)
Treatment (capecitabine)
See Detailed Description.
干预措施: Magnetic Resonance Imaging (Procedure)
Treatment (capecitabine)
See Detailed Description.
干预措施: Questionnaire Administration (Other)
Treatment (capecitabine)
See Detailed Description.
干预措施: Bone Scan (Procedure)
Treatment (capecitabine)
See Detailed Description.
干预措施: Computed Tomography (Procedure)
Treatment (capecitabine)
See Detailed Description.
干预措施: Capecitabine (Drug)
结局指标
主要结局
Ability to achieve adaptive therapy (AT)
时间窗: Up to 5 years
Will be assessed by the proportion of patients (%) who are able to receive 2 or more cycles of AT with capecitabine divided by the total number of patients who have entered the AT phase of treatment (have stable or responsive disease).
次要结局
- Overall survival (OS)(At registration to death up to 5 years)
- Cumulative dose(Up to 5 years)
- Incidence of adverse events (AEs)(Up to 30 days after last dose of study drug)
- Quality of life - EORTC-QLQ-C30(Up to 5 years)
- Time to progression(At registration to disease progression up to 5 years)