Clinical trial NCT03393741: Pharmacodynamic Biomarkers of Standard Anti-microtubule Drugs as Assessed by Early Tumor Biopsy
Official title: Pharmacodynamic Biomarkers of Standard Anti-microtubule Drugs as Assessed by Early Tumor Biopsy
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Breast Cancer
Breast Neoplasms
Keywords: Metastatic breast cancer
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2018-01-08
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Men and women with metastatic or incurable 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Feasibility of measuring biomarkers in advanced breast tumors at 20 +/- 2 hours after chemotherapy
timeFrame: Up to 22 hours
Secondary outcomes:
measure: Measure intratumoral drug levels at 20 +/- 2 hours after chemotherapy
timeFrame: Up to 22 hours
measure: Measure serum drug levels at 20 +/- 2 hours after chemotherapy
timeFrame: Up to 22 hours
measure: Measure PBMC pharmacodynamics at 20 +/- 2 hours after chemotherapy
timeFrame: Up to 22 hours
measure: Assess effects of mitosis and DNA damage response at 20 +/- 2 hours after chemotherapy
timeFrame: Up to 22 hours
measure: Correlate drug levels and cellular effects with response by RECIST 1:1 to chemotherapy
timeFrame: Up to 2 months following completion of study treatment OR upon the systemic imaging following therapy completion (whichever is later)
measure: Assess genomic profile of metastatic breast cancer
timeFrame: Up to 2 months following completion of study treatment OR upon the systemic imaging following therapy completion (whichever is later)
measure: Feasibility of quantifying circulating tumor DNA (ctDNA) 20 +/- 2 hours after administration of chemotherapy.
timeFrame: Up to 2 months following completion of study treatment OR upon the systemic imaging following therapy completion (whichever is later)
measure: Explore differences in progression free survival (PFS) between chemotherapy arms.
timeFrame: Up to 2 months following completion of study treatment OR upon the systemic imaging following therapy completion (whichever is later)
measure: Explore differences in response rate (RR) between chemotherapy arms.
timeFrame: Up to 2 months following completion of study treatment OR upon the systemic imaging following therapy completion (whichever is later)
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Mark Burkard, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: