This is a phase II single-arm, open-label, prospective study to evaluate the efficacy of the low dose weekly Carboplatin/Paclitaxel followed by dose-dense Doxorubicin/Cyclophosphamide in subjects with triple-negative breast cancer in neoadjuvant settings.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
29
Carboplatin is a platinum compound alkylating agent which covalently binds to DNA; interferes with the function of DNA by producing interstrand DNA cross-links.
Paclitaxel promotes microtubule assembly by enhancing the action of tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly, interfering with the late G2 mitotic phase, and inhibiting cell replication. In addition, the drug can distort mitotic spindles, resulting in the breakage of chromosomes. Paclitaxel may also suppress cell proliferation and modulate immune response.
Inhibition of DNA and RNA synthesis by intercalation between DNA base pairs by inhibition of topoisomerase II and by steric obstruction. Doxorubicin intercalates at points of local uncoiling of the double helix. Although the exact mechanism is unclear, it appears that direct binding to DNA (intercalation) and inhibition of DNA repair (topoisomerase II inhibition) result in blockade of DNA and RNA synthesis and fragmentation of DNA. Doxorubicin is also a powerful iron chelator; the iron-doxorubicin complex can bind DNA and cell membranes and produce free radicals that immediately cleave the DNA and cell membranes.
Swedish American Hospital
Rockford, Illinois, United States
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, United States
Columbia St. Mary's Cancer Center
Milwaukee, Wisconsin, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Number and Percentage of Participants With Pathologic Complete Response (pCR) Rate
pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy. pCR will be assessed according to RECIST 1.1 criteria. The point estimate of the primary efficacy endpoint pCR and its exact 95% confidence intervals (CI) will be calculated. In evaluating pCR, subjects with missing data will be considered non-responders.
Time frame: Up to 2 years
Number of Cycles of Chemotherapy Administered
To evaluate the number of cycles low dose weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the number of cycles of chemotherapy administered.
Time frame: Week 12 to week 18 to account for possible delays
Total Dose of Chemotherapy Administered
To evaluate the total dose of weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the dose amount of chemotherapy administered.
Time frame: Week 12 to week 18 to account for possible delays
Delays of Administered Chemotherapy
To evaluate the delays of low dose weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the delays of chemotherapy administered.
Time frame: Week 12 to week 18 to account for possible delays
Number of Treatment-related Toxicities Experienced by Participants
Count of any treatment-related toxicities from the low dose weekly Carboplatin/Paclitaxel regimen. Will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
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Cyclophosphamide is an alkylating agent that prevents cell division by cross-linking DNA strands and decreasing DNA synthesis. It is a cell cycle phase nonspecific agent. Cyclophosphamide also possesses potent immunosuppressive activity. Cyclophosphamide is a prodrug that must be metabolized to active metabolites in the liver.
Pegfilgrastim provides growth factor support in a single dose. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.
Filgrastim provides growth factor support in multiple doses. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.
ProHealth Care
Waukesha, Wisconsin, United States
Aspirus Regional Cancer Center Wausau
Wausau, Wisconsin, United States
Time frame: Up to week 12
Recurrence-free Survival (RFS)
To evaluate two-year RFS after treatment with this neoadjuvant regimen. Count of participants without evidence for local-regional or distant relapse, second primary, or death will be reported.
Time frame: Up to 2 years
Overall Survival (OS)
To evaluate the two-year overall survival after treatment with this neoadjuvant regimen. Count of participants who achieved 2 year OS is reported.
Time frame: Up to 2 years