Neoadjuvant Carbo/Paclitaxel Followed by Doxorubicin/Cyclophosphamide in Breast Cancer
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|ClinicalTrials.gov Identifier: NCT03301350|
Recruitment Status : Suspended (Toxicity)
First Posted : October 4, 2017
Last Update Posted : February 19, 2020
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer Triple Negative Breast Cancer||Drug: Carboplatin Drug: Paclitaxel Drug: Doxorubicin Drug: Cyclophosphamide Drug: Pegfilgrastim Drug: Filgrastim||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Neoadjuvant Carboplatin/Paclitaxel Followed by Dose-Dense Doxorubicin/Cyclophosphamide in Patients With Hormone Receptor Negative, HER2 Receptor Negative Breast Cancer|
|Actual Study Start Date :||November 7, 2017|
|Estimated Primary Completion Date :||October 2022|
|Estimated Study Completion Date :||October 2022|
Experimental: Neoadjuvant Chemotherapy
Regimen A (cycles 1-4):
Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks)
Regimen B (cycles 5-8):
Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)
There is a one week break between the end of cycle 4 and the beginning of cycle 5.
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.
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.
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.
Other Name: cytophosphane
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.
- Pathologic Complete Response (pCR) rate [ Time Frame: Up to 2 years ]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.
- Number of cycles of chemotherapy administered [ Time Frame: Week 12 to week 18 to account for possible delays ]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.
- Total dose of chemotherapy administered [ Time Frame: Week 12 to week 18 to account for possible delays ]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.
- Delays of administered chemotherapy [ Time Frame: Week 12 to week 18 to account for possible delays ]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.
- Number of treatment-related toxicities experienced by participants [ Time Frame: Up to week 12 ]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
- Recurrence-free survival (RFS) [ Time Frame: Up to 2 years ]To evaluate two-year RFS after treatment with this neoadjuvant regimen. Disease-free/recurrence-free survival is defined as the duration for which the participant is without evidence for local-regional or distant relapse, second primary, or death. The median RFS will be obtained by the Kaplan-Meier technique. The 95% confidence interval will be calculated.
- Overall survival (OS) [ Time Frame: Up to 2 years ]To evaluate the two-year overall survival after treatment with this neoadjuvant regimen. OS is defined as the time from initiation of study until death from any cause. The median OS will be obtained by the Kaplan-Meier technique. The 95% confidence interval will be calculated.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03301350
|United States, Illinois|
|Swedish American Hospital|
|Rockford, Illinois, United States, 61104|
|United States, Wisconsin|
|University of Wisconsin Carbone Cancer Center|
|Madison, Wisconsin, United States, 53792|
|Columbia St. Mary's Cancer Center|
|Milwaukee, Wisconsin, United States, 53211|
|Medical College of Wisconsin|
|Milwaukee, Wisconsin, United States, 53226|
|Waukesha, Wisconsin, United States, 53188|
|Aspirus Regional Cancer Center Wausau|
|Wausau, Wisconsin, United States, 54401|
|Principal Investigator:||Kari Wisinski, MD||University of Wisconsin, Madison|