Implantable Microdevice in Testing Drug Sensitivity in Patients with Early Stage, Triple Negative Breast Cancer

PRIMARY OBJECTIVES:

I. To determine the feasibility of implanting and retrieving at least 1 device in patients with early stage triple-negative breast cancer who are candidates for neoadjuvant chemotherapy or upfront surgery.

SECONDARY OBJECTIVES:

I. To describe the safety and possible toxicity of implanting and retrieving at least 1 device in patients with early stage breast cancer who are candidates for neoadjuvant chemotherapy or upfront surgery.

II. To preliminarily assess in vivo chemotherapy sensitivity to doxorubicin hydrochloride and cyclophosphamide (AC) as predicted by the device correlates with residual cancer burden (RCB) 0/1 following standard of care, AC-based neoadjuvant chemotherapy regimen for patients with early stage triple negative breast cancer (TNBC) who receive neoadjuvant therapy (Cohort 2).

III. To evaluate whether in vivo chemotherapy sensitivity to paclitaxel and carboplatin as predicted by the device correlates with RCB 0/1 for patients with early stage TNBC receiving standard of care neoadjuvant chemotherapy with AC followed by paclitaxel + carboplatin (Cohort 2).

IV. To evaluate whether in vivo chemotherapy sensitivity to AC combination at baseline correlates with biomarkers of response in vivo following systemic administration of AC for those patients receiving neoadjuvant therapy.

V. To evaluate the reproducibility of data from replicate drug/drug combinations in each device and across devices in the case where more than one device is retrieved.

VI. To define the inter-observer variability between pathologists for the assessment of phenotypic response in native tumor tissue.

VII. To determine the accuracy by which tissue responses can be co-localized with the specific drug regimens on the microdevice, both in the setting of extracting the device surgically with the entire tumor, as well as extracting the device percutaneously.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT 1 (UPFRONT SURGERY): Patients undergo placement of 3 implantable microdevices into the breast tumor. Beginning 1 day following implantation, the devices are removed with either ultrasound or stereotactic guidance and patients undergo surgery, and receive standard of care adjuvant therapy.

COHORT 2 (NEOADJUVANT THERAPY): Patients undergo placement of 3 implantable microdevices and retrieval as cohort 1. Following retrieval, patients are assigned to 1 of 3 standard of care neoadjuvant anthracycline- based chemotherapy regimen.

I. Patients receive doxorubicin hydrochloride intravenously (IV) and cyclophosphamide IV once every 2 weeks for 4 doses, paclitaxel once weekly for 12 weeks, and carboplatin IV once every 3 weeks for 4 doses.

II. Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV once every 2 weeks for 4 doses, paclitaxel once weekly for 12 weeks, and carboplatin IV once weekly for 12 doses.

III. Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV once every 2 weeks for 4 doses.

Within 4 weeks of the last dose of neoadjuvant chemotherapy, patients undergo definitive surgery.