Pharmacodynamic Biomarkers of Standard Anti-microtubule Drugs as Assessed by Early Tumor Biopsy
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Feasibility of measuring biomarkers in advanced breast tumors at 20 +/- 2 hours after chemotherapy
研究概览
简要总结
Eligible subjects will be assigned to study treatment arms by their treating oncologist, rather than by the study. The drug, dose, and schedule of administration will be determined by the treating physician per NCCN guidelines for standard of care chemotherapy regimens for recurrent or metastatic breast cancer. Study treatment arms include: Taxane (nab-paclitaxel or paclitaxel), Eribulin, Vinorelbine, Ixabepilone, or the control arm (non-microtubule targeted chemotherapies such as doxorubicin, carboplatin, or gemcitabine).
详细描述
During the screening visit, the following will be taken: medical history; physical exam; ECOG performance status; a pregnancy test if indicated per physician (confirmation of the clinical testing result or assessment of the treating physician whether or not the subject is capable of pregnancy); AST, ALT, CBC (per oncologist); 15 mL blood sample for drug level assessment; 15 mL blood sample for circulating tumor DNA (ctDNA); follow up assessments of cancer; RECIST 1.1 response measurements; and an archived FFPE sample (8 slides) will be obtained.
While enrolled on study, subjects will have the following procedures:
- 15 mL blood sample for drug level assessment on C1D2
- 15 mL blood sample for circulating tumor DNA (ctDNA) on C1D2 and at progression or end of study for a total of 30 mL
- Adverse events related to study procedures (research biopsy & blood draws) will be assessed on C1D2 and at progression or end of study
- Toxicity evaluations will occur throughout the study per the treating MD
- Follow-up assessments of cancer will occur throughout the study per the treating MD
- RECIST 1.1 response measurements will be taken at standard of care imaging
- Fresh biopsy or tumor sampling (4 cores) for analysis of intratumoral drug levels and biomarkers including: markers of proliferation (mitotic index), aneuploidy, and sequencing analysis (ctDNA) on C1D2.
The tests being performed on the samples as part of this study are not investigational.
Subjects will be followed with imaging scans and tumor markers as deemed appropriate by the treating physician. Follow-up scans will be recommended every ~3 cycles as per standard of care. Subjects will be followed for the duration of treatment initiated while taking part in this study. Follow-up will discontinue either 2 months following completion of planned breast cancer treatment or upon the systemic imaging following therapy completion (whichever is later).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Men and women with histologically or cytologically demonstrated breast cancer that is deemed metastatic or incurable by the treating physician.
- •It is medically appropriate to treat the patient with an antimitotic agent or an intravenous control chemotherapeutic agent by IV infusion at standard doses as per the treating physician. Please see NCCN guidelines for standard of care, p58 for standard chemotherapy regimens for recurrent or metastatic breast cancer
- •The patient has measureable disease as determined by RECIST 1.
- •Archived tissue is available from either primary, metastatic site or both.
- •It is safe and feasible to obtain a research tumor biopsy on cycle 1 day 2 with a biopsy of an accessible lesion such as liver, lung, lymph node, skin, breast, or bone.
- •All pre-chemotherapy test results (tests per treating oncologist discretion) have been reviewed and deemed appropriate for planned chemotherapy by the patient's treating oncologist.
排除标准
- •HER2+ breast cancer by standard criteria.
- •Pregnant women are excluded from this study because systemic chemotherapy may cause deleterious effects to the fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with systemic chemotherapy, breastfeeding should be discontinued if the mother is enrolled in the trial.
- •Planned treatment with hormonal therapy, or targeted oral therapy during trial enrollment.
研究组 & 干预措施
Taxane (nab-paclitaxel or paclitaxel)
Up to 10 participants will be enrolled on the Taxane arm. The dose and schedule of administration is determined by the treating physician. The first dose will be coordinated in conjunction with research staff who will schedule a research biopsy to be completed on Day 2 of the first planned chemotherapy treatment cycle (C1D2). Participants are not eligible for replacement as long as they are able to have the C1D2 biopsy completed.
Two tubes of blood of up to 15ml each drawn prior to chemotherapy and again just before or after research biopsy on C1D2. A 15ml sample of blood drawn at the time subject comes off study or at the time of disease progression.
Tumor core biopsy is obtained as close as possible to 20 hours following initiation of the first planned treatment infusions. Between 2 and 4 cores will be obtained for research biopsy.
干预措施: Taxane (Drug)
Taxane (nab-paclitaxel or paclitaxel)
Up to 10 participants will be enrolled on the Taxane arm. The dose and schedule of administration is determined by the treating physician. The first dose will be coordinated in conjunction with research staff who will schedule a research biopsy to be completed on Day 2 of the first planned chemotherapy treatment cycle (C1D2). Participants are not eligible for replacement as long as they are able to have the C1D2 biopsy completed.
Two tubes of blood of up to 15ml each drawn prior to chemotherapy and again just before or after research biopsy on C1D2. A 15ml sample of blood drawn at the time subject comes off study or at the time of disease progression.
Tumor core biopsy is obtained as close as possible to 20 hours following initiation of the first planned treatment infusions. Between 2 and 4 cores will be obtained for research biopsy.
干预措施: Chemotherapy (Drug)
Eribulin
Up to 5 participants will be enrolled on the Eribulin arm. The dose and schedule of administration is determined by the treating physician. The first dose will be coordinated in conjunction with research staff who will schedule a research biopsy to be completed on Day 2 of the first planned chemotherapy treatment cycle (C1D2). Participants are not eligible for replacement as long as they are able to have the C1D2 biopsy completed.
Two tubes of blood of up to 15ml each drawn prior to chemotherapy and again just before or after research biopsy on C1D2. A 15ml sample of blood drawn at the time subject comes off study or at the time of disease progression.
Tumor core biopsy is obtained as close as possible to 20 hours following initiation of the first planned treatment infusions. Between 2 and 4 cores will be obtained for research biopsy.
干预措施: Eribulin (Drug)
Eribulin
Up to 5 participants will be enrolled on the Eribulin arm. The dose and schedule of administration is determined by the treating physician. The first dose will be coordinated in conjunction with research staff who will schedule a research biopsy to be completed on Day 2 of the first planned chemotherapy treatment cycle (C1D2). Participants are not eligible for replacement as long as they are able to have the C1D2 biopsy completed.
Two tubes of blood of up to 15ml each drawn prior to chemotherapy and again just before or after research biopsy on C1D2. A 15ml sample of blood drawn at the time subject comes off study or at the time of disease progression.
Tumor core biopsy is obtained as close as possible to 20 hours following initiation of the first planned treatment infusions. Between 2 and 4 cores will be obtained for research biopsy.
干预措施: Chemotherapy (Drug)
Vinorelbine
Up to 5 participants will be enrolled on the Vinorelbine arm. TThe dose and schedule of administration is determined by the treating physician. The first dose will be coordinated in conjunction with research staff who will schedule a research biopsy to be completed on Day 2 of the first planned chemotherapy treatment cycle (C1D2). Participants are not eligible for replacement as long as they are able to have the C1D2 biopsy completed.
Two tubes of blood of up to 15ml each drawn prior to chemotherapy and again just before or after research biopsy on C1D2. A 15ml sample of blood drawn at the time subject comes off study or at the time of disease progression.
Tumor core biopsy is obtained as close as possible to 20 hours following initiation of the first planned treatment infusions. Between 2 and 4 cores will be obtained for research biopsy.
干预措施: Vinorelbine (Drug)
Vinorelbine
Up to 5 participants will be enrolled on the Vinorelbine arm. TThe dose and schedule of administration is determined by the treating physician. The first dose will be coordinated in conjunction with research staff who will schedule a research biopsy to be completed on Day 2 of the first planned chemotherapy treatment cycle (C1D2). Participants are not eligible for replacement as long as they are able to have the C1D2 biopsy completed.
Two tubes of blood of up to 15ml each drawn prior to chemotherapy and again just before or after research biopsy on C1D2. A 15ml sample of blood drawn at the time subject comes off study or at the time of disease progression.
Tumor core biopsy is obtained as close as possible to 20 hours following initiation of the first planned treatment infusions. Between 2 and 4 cores will be obtained for research biopsy.
干预措施: Chemotherapy (Drug)
Ixabepilone
Up to 5 participants will be enrolled on the Ixabepilone arm. The dose and schedule of administration is determined by the treating physician. The first dose will be coordinated in conjunction with research staff who will schedule a research biopsy to be completed on Day 2 of the first planned chemotherapy treatment cycle (C1D2). Participants are not eligible for replacement as long as they are able to have the C1D2 biopsy completed.
Two tubes of blood of up to 15ml each drawn prior to chemotherapy and again just before or after research biopsy on C1D2. A 15ml sample of blood drawn at the time subject comes off study or at the time of disease progression.
Tumor core biopsy is obtained as close as possible to 20 hours following initiation of the first planned treatment infusions. Between 2 and 4 cores will be obtained for research biopsy.
干预措施: Ixabepilone (Drug)
Ixabepilone
Up to 5 participants will be enrolled on the Ixabepilone arm. The dose and schedule of administration is determined by the treating physician. The first dose will be coordinated in conjunction with research staff who will schedule a research biopsy to be completed on Day 2 of the first planned chemotherapy treatment cycle (C1D2). Participants are not eligible for replacement as long as they are able to have the C1D2 biopsy completed.
Two tubes of blood of up to 15ml each drawn prior to chemotherapy and again just before or after research biopsy on C1D2. A 15ml sample of blood drawn at the time subject comes off study or at the time of disease progression.
Tumor core biopsy is obtained as close as possible to 20 hours following initiation of the first planned treatment infusions. Between 2 and 4 cores will be obtained for research biopsy.
干预措施: Chemotherapy (Drug)
Control Arm
Up to 10 participants will be enrolled on the control arm. The dose and schedule of administration is determined by the treating physician. The first dose will be coordinated in conjunction with research staff who will schedule a research biopsy to be completed on Day 2 of the first planned chemotherapy treatment cycle (C1D2). Participants are not eligible for replacement as long as they are able to have the C1D2 biopsy completed.
Two tubes of blood of up to 15ml each drawn prior to chemotherapy and again just before or after research biopsy on C1D2. A 15ml sample of blood drawn at the time subject comes off study or at the time of disease progression.
Tumor core biopsy is obtained as close as possible to 20 hours following initiation of the first planned treatment infusions. Between 2 and 4 cores will be obtained for research biopsy.
干预措施: Chemotherapy (Drug)
结局指标
主要结局
Feasibility of measuring biomarkers in advanced breast tumors at 20 +/- 2 hours after chemotherapy
时间窗: Up to 22 hours
Advanced breast tumors safely sampled and analyzed from 35 subjects. In order to successfully test the hypothesis that chromosomal instability in part governs the effect of antimitotic therapies, advanced breast tumors samples must be collected, preserved, and analyzed at 20+/- 2 hours after chemotherapy in order to characterize the effect of the drug on the tumor. A primary question becomes is this process safe and feasible within these time constraints in our clinical setting.
次要结局
- Measure PBMC pharmacodynamics at 20 +/- 2 hours after chemotherapy(Up to 22 hours)
- Assess genomic profile of metastatic breast cancer(Up to 2 months following completion of study treatment OR upon the systemic imaging following therapy completion (whichever is later))
- Explore differences in progression free survival (PFS) between chemotherapy arms.(Up to 2 months following completion of study treatment OR upon the systemic imaging following therapy completion (whichever is later))
- Measure serum drug levels at 20 +/- 2 hours after chemotherapy(Up to 22 hours)
- Measure intratumoral drug levels at 20 +/- 2 hours after chemotherapy(Up to 22 hours)
- Correlate drug levels and cellular effects with response by RECIST 1:1 to chemotherapy(Up to 2 months following completion of study treatment OR upon the systemic imaging following therapy completion (whichever is later))
- Explore differences in response rate (RR) between chemotherapy arms.(Up to 2 months following completion of study treatment OR upon the systemic imaging following therapy completion (whichever is later))
- Assess effects of mitosis and DNA damage response at 20 +/- 2 hours after chemotherapy(Up to 22 hours)
- Feasibility of quantifying circulating tumor DNA (ctDNA) 20 +/- 2 hours after administration of chemotherapy.(Up to 2 months following completion of study treatment OR upon the systemic imaging following therapy completion (whichever is later))