Breast Cancer, Breast Neoplasms
Conditions
Keywords
Metastatic breast cancer
Brief summary
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).
Detailed description
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).
Interventions
DRUGTaxane
Taxane is a chemotherapeutic agent and a standard drug for treatment in breast cancer targeting microtubules. This drug is typically infused as a single agent for breast cancer therapy.
DRUGVinorelbine
Vinorelbine is a chemotherapeutic agent and a standard drug for treatment in breast cancer targeting microtubules. This drug is typically infused as a single agent for breast cancer therapy.
DRUGIxabepilone
Ixabepilone is a chemotherapeutic agent and a standard drug for treatment in breast cancer targeting microtubules. This drug is typically infused as a single agent for breast cancer therapy.
DRUGEribulin
Eribulin is a chemotherapeutic agent and a standard drug for treatment in breast cancer targeting microtubules. This drug is typically infused as a single agent for breast cancer therapy.
DRUGChemotherapy
Chemotherapy is used to treat various stages of breast cancer.
Sponsors
National Cancer Institute (NCI)
University of Wisconsin, Madison
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 cancer7. * The patient has measureable disease as determined by RECIST 1.1. * 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of measuring biomarkers in advanced breast tumors at 20 +/- 2 hours after chemotherapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure serum drug levels at 20 +/- 2 hours after chemotherapy | Up to 22 hours | Tumor tissue and plasma samples taken at 20 hours will be assessed for drug levels by the University of Wisconsin 3P Lab. |
| Measure PBMC pharmacodynamics at 20 +/- 2 hours after chemotherapy | Up to 22 hours | Tumor tissue and plasma samples taken at 20 hours will be assessed for drug levels by the University of Wisconsin 3P Lab. |
| Assess effects of mitosis and DNA damage response at 20 +/- 2 hours after chemotherapy | Up to 22 hours | Mitotic index will be analyzed by fluorescence in situ hybridization, immunofluorescence, immunohistochemistry, and liquid chromatography and ctDNA |
| 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) | Summary statistics will be used to describe drug levels and cellular effects by response to chemotherapy |
| Measure intratumoral drug levels at 20 +/- 2 hours after chemotherapy | Up to 22 hours | Tumor tissue and plasma samples taken at 20 hours will be assessed for drug levels by the University of Wisconsin 3P Lab. |
| 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) | This measurement is taken to understand if changes in ctDNA over the stated interval can be correlated to the treatment response and genomic profile from the 35 subjects. |
| 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) | PFS will be analyzed using the Kaplan-Meier method and measured from C1D1 until documented progression on imaging scan or death. Patients who do not experience documented progression during the study and are alive at last follow-up will be censored on the date of last imaging scan. Small sample statistical methods will be used to compare PFS curves by chemotherapy arm. |
| 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) | Response rate (RR) will be summarized by chemotherapy arm including 95% confidence intervals. |
| 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) | This sequencing is measured to understand how changes in treatment response correlate to genomic profile. |
Countries
United States
Outcome results
None listed