Neoadjuvant Carbo/Paclitaxel Followed by Doxorubicin/Cyclophosphamide in Breast Cancer

NCT03301350 | Completed Phase 2 Results DMC FDA Drug

• 5 other identifiers: 2017-0547NCI-2017-01705A534260SMPH\MEDICINE\HEM-ONCProtocol Version 11/26/2019
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Breast Cancer; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 2 years

Secondary Outcomes (6)

• Number of Cycles of Chemotherapy Administered

  Week 12 to week 18 to account for possible delays

• Total Dose of Chemotherapy Administered

  Week 12 to week 18 to account for possible delays

• Delays of Administered Chemotherapy

  Week 12 to week 18 to account for possible delays

• Number of Treatment-related Toxicities Experienced by Participants

  Up to week 12

• Recurrence-free Survival (RFS)

  Up to 2 years

Study Arms (1)

Neoadjuvant Chemotherapy

EXPERIMENTAL

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. Regimen C: Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.

Drug: Carboplatin; Drug: Paclitaxel; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Pegfilgrastim; Drug: Filgrastim

Interventions

Carboplatin DRUG

Carboplatin is a platinum compound alkylating agent which covalently binds to DNA; interferes with the function of DNA by producing interstrand DNA cross-links.

Neoadjuvant Chemotherapy

Paclitaxel DRUG

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.

Neoadjuvant Chemotherapy

Doxorubicin DRUG

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.

Also known as: Adriamycin, Doxil, Caelyx, Myocet

Neoadjuvant Chemotherapy

Cyclophosphamide DRUG

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.

Also known as: cytophosphane

Neoadjuvant Chemotherapy

Pegfilgrastim DRUG

Pegfilgrastim provides growth factor support in a single dose. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.

Neoadjuvant Chemotherapy

Filgrastim DRUG

Filgrastim provides growth factor support in multiple doses. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.

Neoadjuvant Chemotherapy

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have histologically or cytologically confirmed invasive breast cancer which meets the following criteria:
• Estrogen Receptor (ER) and Progesterone Receptor (PR)-negative as defined by local standard clinical immunohistochemistry (IHC) \< 1%.
• HER2-negative using local standard testing. Negative is defined as IHC 0 or 1+ (if 2+, must reflex to ISH method). If ISH method is used, ratio \< 2 is considered negative.
• Clinical tumor size of at least 2.1 cm (T2) by palpation or imaging, regardless of the ipsilateral regional lymph node status, or any tumor size but with ipsilateral regional lymph nodes involved by the tumor (any T if ipsilateral regional node positive). Subjects with inflammatory breast cancer are eligible. If bilateral breast cancer is present, the subject is eligible if the contralateral tumor is DCIS only (without any invasive disease on biopsy) or another invasive breast cancer of any size that is also ER, PR and HER2 negative.
• Any radiographic abnormal ipsilateral regional lymph nodes or any clinically concerning ipsilateral regional lymph nodes with the exception of internal mammary nodes should be sampled with percutaneous biopsy, but no sentinel axillary lymph node mapping/biopsy is allowed before chemotherapy. If clinically node negative (cNO), pre-chemotherapy ipsilateral sentinel axillary lymph node mapping/biopsy is not allowed.
• Candidate for neoadjuvant chemotherapy.
• Age \> 18 years and \< 75 years
• ECOG Performance Status \< 1.
• Left ventricular ejection fraction (LVEF) ≥ LLN (per institutional normal) determined by
• Adequate organ and marrow function as determined by study protocol
• Non Pregnant. Women of childbearing potential must have a negative pregnancy test (HCG serum or urine) within 30 days prior to study registration and to be repeated if not done within 7 days of starting chemotherapy.
• Female subjects must meet one of the following:
• Natural postmenopausal before the screening visit defined as no menses at any time in the preceding 12 consecutive months, or
• Prior bilateral oophorectomy or bilateral tubal ligation, or
• If they are of childbearing potential, agree to practice two effective methods of contraception per discussion with the treating physicians from

You may not qualify if:

• Prior chemotherapy or radiation therapy for invasive breast cancer within 6 months before registration.
• Prior investigational drugs or interventions for invasive breast cancer within 6 months before registration are not allowed. Prior participation in window-of-opportunity trials without therapeutic intent is allowed if intervention is no more than 3 weeks duration.
• Stage IV metastatic breast cancer
• History of allergic reactions attributed to compounds of similar chemical composition to chemotherapy to be used in this study.
• Breastfeeding women. Cytotoxic chemotherapy is drug with the potential for teratogenic or abortifacient effects. Due to unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cytotoxic chemotherapy, breastfeeding should be discontinued.
• Baseline peripheral neuropathy of severity \> grade 1
• Other invasive cancer diagnosis within the past 5 years other than non-melanoma skin cancer.
• Prior axillary lymph node dissection that preclude patient from surgical evaluation of axillary lymph node status.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (6)

Swedish American Hospital

Rockford, Illinois, 61104, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Columbia St. Mary's Cancer Center

Milwaukee, Wisconsin, 53211, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

ProHealth Care

Waukesha, Wisconsin, 53188, United States

Location

Aspirus Regional Cancer Center Wausau

Wausau, Wisconsin, 54401, United States

Location

Related Links

• UW Carbone Cancer Center home page

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Carboplatin; Paclitaxel; Doxorubicin; liposomal doxorubicin; Cyclophosphamide; pegfilgrastim; Filgrastim

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

Complete AE data was not collected; approximately 40% of participants are represented in the data reported in the Adverse Events section. Some enrolling sites have been chronically under- and un-staffed for 2+ years, and have not been able to address the coordinating center's numerous queries related to AE data.

Results Point of Contact

• Title: Kari Wisinski, MD
• Organization: University of Wisconsin Carbone Cancer Center

kbwisinski@medicine.wisc.edu

608-262-2876

Study Officials

• Kari Wisinski, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2017
• First Posted: October 4, 2017
• Study Start: November 7, 2017
• Primary Completion: March 23, 2020
• Study Completion: February 7, 2022
• Last Updated: February 13, 2026
• Results First Posted: February 1, 2023

Record last verified: 2023-01

Locations

US (6)