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

NCT ID: NCT03301350

Last Updated: 2023-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-07
• Study Completion Date: 2022-02-07

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Regimen C:

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

Group Type: EXPERIMENTAL

Carboplatin

Intervention Type: 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.

Paclitaxel

Intervention Type: 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.

Doxorubicin

Intervention Type: 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.

Cyclophosphamide

Intervention Type: 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.

Pegfilgrastim

Intervention Type: DRUG

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

Filgrastim

Intervention Type: DRUG

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

Interventions

Carboplatin

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

Intervention Type: DRUG

Paclitaxel

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.

Intervention Type: DRUG

Doxorubicin

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.

Intervention Type: DRUG

Cyclophosphamide

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.

Intervention Type: DRUG

Pegfilgrastim

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

Intervention Type: DRUG

Filgrastim

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

Intervention Type: DRUG

Other Intervention Names

Adriamycin; Doxil; Caelyx; Myocet; cytophosphane

Eligibility Criteria

Inclusion Criteria

1. Subjects must have histologically or cytologically confirmed invasive breast cancer which meets the following criteria:

1. Estrogen Receptor (ER) and Progesterone Receptor (PR)-negative as defined by local standard clinical immunohistochemistry (IHC) < 1%.

2. 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.

3. 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.

4. 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.

2. Candidate for neoadjuvant chemotherapy.

3. Age > 18 years and < 75 years

4. ECOG Performance Status < 1.

5. Left ventricular ejection fraction (LVEF) ≥ LLN (per institutional normal) determined by

6. Adequate organ and marrow function as determined by study protocol

7. 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.

1. 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

2. Male subjects, even if surgically sterilized (i.e., status post vasectomy) must agree to one of the following:

• Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose, or
• Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)

8. Ability to understand a written informed consent document, and the willingness to sign it.

Exclusion Criteria

1. Prior chemotherapy or radiation therapy for invasive breast cancer within 6 months before registration.

2. 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.

3. Stage IV metastatic breast cancer

4. History of allergic reactions attributed to compounds of similar chemical composition to chemotherapy to be used in this study.

5. 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.

6. Baseline peripheral neuropathy of severity > grade 1

7. Other invasive cancer diagnosis within the past 5 years other than non-melanoma skin cancer.

8. Prior axillary lymph node dissection that preclude patient from surgical evaluation of axillary lymph node status.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kari Wisinski, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

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

ProHealth Care

Waukesha, Wisconsin, United States

Aspirus Regional Cancer Center Wausau

Wausau, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.uwhealth.org/uw-carbone-cancer-center/47424

UW Carbone Cancer Center home page

Other Identifiers

NCI-2017-01705

Identifier Type: REGISTRY

Identifier Source: secondary_id

2017-0547

Identifier Type: OTHER

Identifier Source: secondary_id

A534260

Identifier Type: OTHER

Identifier Source: secondary_id

SMPH\MEDICINE\HEM-ONC

Identifier Type: OTHER

Identifier Source: secondary_id

Protocol Version 11/26/2019

Identifier Type: OTHER

Identifier Source: secondary_id

UW16112

Identifier Type: -

Identifier Source: org_study_id