Neoadjuvant Carbo/Paclitaxel Followed by Doxorubicin/Cyclophosphamide in Breast Cancer
Condition: Breast Cancer; Triple Negative Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: Carboplatin; Paclitaxel; Doxorubicin; Cyclophosphamide; Pegfilgrastim; Filgrastim
Intervention description: 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.; 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.
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Carboplatin; Doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Maximum age: 74 Years
Healthy volunteers: No

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.
    

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.