Clinical Trials /

Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Before Surgery in Treating Patients With Locally Advanced or Inflammatory Triple Negative Breast Cancer

NCT01525966

Description:

This phase II trial studies how well carboplatin and nab-paclitaxel before surgery work in treating patients with triple negative breast cancer that is inflammatory or has spread from where it started to nearby tissue or lymph nodes. Drugs used in chemotherapy, such as carboplatin and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Carboplatin</span> and <span class="go-doc-concept go-doc-intervention">Paclitaxel Albumin-Stabilized Nanoparticle Formulation</span> Before Surgery in Treating Patients With Locally Advanced or Inflammatory <span class="go-doc-concept go-doc-keyword">Triple Negative</span> Breast Cancer

Title

  • Brief Title: Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Before Surgery in Treating Patients With Locally Advanced or Inflammatory Triple Negative Breast Cancer
  • Official Title: Phase II Trial of Neoadjuvant Chemotherapy With Carboplatin and NAB-Paclitaxel in Patients With Locally Advanced and Inflammatory Triple Negative Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT01525966

    ORG ID: 11174

    NCI ID: NCI-2012-00025

    Trial Conditions

    Inflammatory Breast Cancer

    Stage II Breast Cancer

    Stage IIIA Breast Cancer

    Stage IIIB Breast Cancer

    Stage IIIC Breast Cancer

    Triple-negative Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    carboplatin Carboplat, CBDCA, JM-8, Paraplat, Paraplatin Treatment (chemotherapy)
    paclitaxel albumin-stabilized nanoparticle formulation ABI-007, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxel Treatment (chemotherapy)

    Trial Purpose

    This phase II trial studies how well giving carboplatin and paclitaxel albumin-stabilized
    nanoparticle formulation together before surgery works in treating patients with locally
    advanced or inflammatory triple negative breast cancer. Drugs used in chemotherapy, such as
    carboplatin and paclitaxel albumin-stabilized nanoparticle formulation, work in different
    ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
    dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the
    amount of normal tissue that needs to be removed.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To test the hypothesis that carboplatin + nab-paclitaxel (paclitaxel albumin-stabilized
    nanoparticle formulation) therapy will demonstrate a promising neoadjuvant pathologic
    complete response (pCR) rate for eligible patients.

    II. To test the hypothesis that carboplatin + nab-paclitaxel therapy will demonstrate a
    promising Symmans 0-1 pathological response rate for eligible patients.

    SECONDARY OBJECTIVES:

    I To evaluate the overall survival and event-free survival of eligible patients treated with
    carboplatin + nab-paclitaxel neoadjuvant chemotherapy.

    II. To evaluate the toxicities and tolerance of carboplatin + nab-paclitaxel therapy in this
    patient population.

    III. To evaluate the role of laboratory correlates in response, toxicity and survival
    endpoints.

    IV. To procure tissue and perform analysis of gene and protein expression profiles of
    pre-treatment primary tumor (estimated success rate: 80%) and residual tumors (25%) and
    lymph nodes including the study of tumor niche (50%), studying sequential assessment of
    cellular characteristics and gene and protein expression profiles.

    V. To identify specific mutations in tumor deoxyribonucleic acid (DNA) in comparison to
    adjacent tissue and germ line DNA procured prior to, during, and subsequent to neoadjuvant
    chemotherapy, and to detect/measure, as feasible, the presence of such mutations in
    fragmented circulating DNA from plasma, and to correlate these mutations with the
    presence/characteristics of circulating tumor cells in order to identify prognostic and
    predictive indicators of persisting/relapsed disease and targets for therapy.

    VI. To assess ribonucleic acid (RNA) (using Mammaprint/Blueprint and 44,000 Agilent platform
    gene array), (micro) miRNA and protein profiles in tumor, adjacent tissue and plasma prior
    to, during, and at completion of neoadjuvant chemotherapy in order to establish prognostic
    and predictive indicators of outcome, markers of persistent/relapsed disease, and targets
    for therapy.

    VII. To analyze tumor DNA and genomic DNA from plasma by microarray and reverse
    transcriptase (RT)-polymerase chain reaction (PCR) analysis to assess copy numbers/single
    nucleotide polymorphisms (SNP)/genomic polymorphisms in genes for the purposes of
    establishing prognostic and predictive indicators of outcomes; markers of
    persistence/relapse disease, drug resistance, and drug metabolism; and targets of therapy.

    VIII. To assess the prognostic and predictive value of conventional pathological features
    (stage, estrogen and progesterone receptor and human epidermal growth factor receptor
    [HER-2] status, presence of lymphovascular invasion, high grade tumor status) in comparison
    to such values derived from the molecular approaches.

    IX. To procure tumor from the primary and definitive surgical specimen for the purpose of
    establishing breast cancer stem cell lines.

    X. To procure blood samples for the purpose of identifying and characterizing circulating
    tumor cells.

    OUTLINE: Patients receive carboplatin intravenously (IV) over 30 minutes on day 1 and
    paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once weekly.
    Treatment repeats every 28 days for 4 courses in the absence of disease progression or
    unacceptable toxicity.

    After completion of study treatment, patients are followed up every 3 months for 4 years and
    then every 6 months for 1 year.

    Trial Arms

    Name Type Description Interventions
    Treatment (chemotherapy) Experimental Patients receive carboplatin IV over 30 minutes on day 1 and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once weekly. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. carboplatin, paclitaxel albumin-stabilized nanoparticle formulation

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must be diagnosed with locally advanced (T2 and higher with or without lymph
    node involvement), and/or inflammatory triple negative breast cancer

    - Women of child-bearing potential and men must agree to use adequate contraception
    (hormonal or barrier method of birth control or abstinence) prior to study entry and
    for six months following duration of study participation; should a woman become
    pregnant or suspect that she is pregnant while participating on the trial, she should
    inform her treating physician immediately

    - Tumor negative for expression of hormone receptors (< 1%) and not over-expressing
    HER2 by immunohistochemistry (IHC) (0-1), or in case of IHC of 2, negative by
    fluorescence in situ hybridization (FISH) or by alternative gene testing

    - Bilirubin =< 1.5 mg/dL

    - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2 x upper
    limit of normal

    - Alkaline phosphatase =< 2 x upper limit of normal

    - Platelets >= 100,000 cells/mm^3

    - Hemoglobin > 9.0 g/dL

    - Absolute neutrophil count (ANC) >= 1,500 cells/mm^3

    - Creatinine =< 1.5 mg/dL is recommended; however, institutional norms are acceptable

    - Left ventricular ejection fraction > 50%

    - Women of childbearing potential and sexually active males must use an effective
    contraception method during treatment and for three months after completing treatment

    - Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test
    screening for patients of childbearing potential

    - All subjects must have the ability to understand and the willingness to sign a
    written informed consent

    - No prior therapies are allowed for the treatment of the newly diagnosed breast
    cancer; patients with a prior diagnosis of malignancy treated >= 5 years ago are
    eligible, provided that they have not received prior taxanes or carboplatin as part
    of their prior treatment regimen, and that they meet all eligibility criteria

    Exclusion Criteria:

    - Known active hepatitis B or C

    - Known active human immunodeficiency virus (HIV)

    - Prior breast cancer or other invasive malignancy treated within 5 years

    - Pregnancy

    - Neuropathy > grade 1

    - Any other intercurrent medical/psychological problem deemed exclusionary by the
    treating physician or investigators/primary investigator (PI)

    - Subjects will be excluded who, in the opinion of the investigator, may not be able to
    comply with the safety monitoring requirements of the study

    Minimum Eligible Age: 19 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    pCR or Symmans 0-1 pathological response

    Secondary Outcome Measures

    Overall survival

    Progression-free survival

    Number of patients experiencing serious adverse events (SAEs) graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Trial Keywords