Clinical Trials /

Neoadjuvant Study of Two Platinum Regimens in Triple Negative Breast Cancer

NCT02413320

Description:

Evaluate if the two carboplatin containing chemotherapy regimens will reduce the growth of breast cancer cells in women with Stage I, II, or III triple negative breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Neoadjuvant <span class="go-doc-concept go-doc-intervention">Carboplatin</span> and <span class="go-doc-concept go-doc-intervention">Docetaxel</span> in TNBC

Title

  • Brief Title: Neoadjuvant Carboplatin and Docetaxel in TNBC
  • Official Title: Randomized, Open Label, Phase II Trial of Neoadjuvant Carboplatin Plus Docetaxel or Carboplatin Plus Paclitaxel Followed by AC in Stage I-III Triple-negative Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02413320

    ORG ID: 2014-BRST-TNBC-LQT

    Trial Conditions

    Triple-negative Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Paclitaxel taxol Carboplatin + Paclitaxel then Doxorubicin + Cyclophosphamide
    Carboplatin paraplatin Carboplatin + Paclitaxel then Doxorubicin + Cyclophosphamide, Carboplatin + Docetaxel
    Doxorubicin adriamycin Carboplatin + Paclitaxel then Doxorubicin + Cyclophosphamide
    Cyclophosphamide cytoxin, procytox Carboplatin + Paclitaxel then Doxorubicin + Cyclophosphamide
    Docetaxel taxotere Carboplatin + Docetaxel

    Trial Purpose

    Evaluate if the two carboplatin containing chemotherapy regimens will reduce the growth of
    breast cancer cells in women with Stage I, II, or III triple negative breast cancer.

    Detailed Description

    Sporadic and germline BRCA mutation associated triple-negative breast cancer share several
    pathological and molecular similarities which have led to the exploration of DNA damaging
    agents like platinum compounds in patients with triple-negative breast cancer. Recent
    studies demonstrate that addition of neoadjuvant carboplatin to
    doxorubicin/cyclophosphamide/taxane-based chemotherapy improves pathological complete
    response in patients with stage I-III triple-negative breast cancer but also increase
    toxicity.

    A recent study reported encouraging pathological complete response rates with a
    non-anthracycline carboplatin plus docetaxel neoadjuvant chemotherapy regimen in a cohort of
    49 triple negative breast cancer patients. This chemotherapy regimen of carboplatin plus
    docetaxel yielded an overall pathological complete response rate of 65% in unselected
    triple-negative breast cancer with pathological complete response rates of 61% in sporadic
    and 77% in germline BRCA-associated triple-negative breast cancer. The chemotherapy regimen
    of carboplatin/docetaxel is well tolerated and should be studied further and compared with
    regimens that add carboplatin to the standard anthracycline/taxane containing regimens.

    This is the basis for the proposed randomized neoadjuvant phase II study to further estimate
    and compare pathological complete response rates of carboplatin plus docetaxel x 6 cycles to
    carboplatin plus paclitaxel x 4 cycles followed by doxorubicin plus cyclophosphamide x 4
    cycles in stage I-III triple negative-breast cancer.

    Trial Arms

    Name Type Description Interventions
    Carboplatin + Paclitaxel then Doxorubicin + Cyclophosphamide Active Comparator Paclitaxel (80mg/m2) given IV every week x12 weeks and Carboplatin (AUC 6) given IV every 21 days x 4 cycles, followed by Doxorubicin (60mg/m2) given IV and Cyclophosphamide (600mg/m2) given IV every 14 days X 4 cycles Paclitaxel, Carboplatin, Doxorubicin, Cyclophosphamide
    Carboplatin + Docetaxel Active Comparator Carboplatin (AUC 6) given IV and Docetaxel (75mg/m2) given IV every 21 days x 6 cycles Carboplatin, Docetaxel

    Eligibility Criteria

    Inclusion Criteria:

    - Patients with newly diagnosed stage I (T>1cm), II or III triple negative breast
    cancer who have not had definitive breast surgery or received systemic chemotherapy

    - The invasive tumor must be hormone receptor-poor, defined as both estrogen receptor
    and progesterone receptor staining present in < 10% of invasive cancer cells by
    Immunohistochemistry.

    - HER- 2 negativity will be based on the current ASCO-CAP guidelines for HER testing

    - No prior chemotherapy, endocrine therapy or radiation therapy with therapeutic intent
    for this cancer

    - Female subjects age 18 - 70 years

    - ECOG Performance Status of 0-1

    - Adequate organ and marrow function as defined below:

    - Leukocytes 3,000/uL

    - Absolute neutrophil count 1500/uL

    - Platelets 100,000/uL

    - Total bilirubin 1.5mg/dL

    - AST(SGOT)/ALT(SPGT) 2 x institutional upper limit of normal

    - Creatinine 1.5mg/dl and/or Creatinine Clearance 60mL/min

    - Serum albumin > 3.0 g/dL

    - Women of child-bearing potential must agree to use adequate contraception .

    - Subjects in Arm A should have LVEF 50% by echocardiogram or MUGA scan performed
    within 4 weeks prior to treatment initiation

    - Subjects should have breast and axillary imaging with breast MRI or breast and
    axillary ultrasound within 4 weeks prior to treatment initiation

    - Subjects with clinically/radiologically abnormal axillary lymph nodes should have
    pathological confirmation of disease with image guided biopsy/fine needle aspiration.

    - Subjects must be already enrolled in P.R.O.G.E.C.T observational registry

    - Staging to rule out metastatic disease is recommended for subjects with clinical
    stage III disease

    - Subjects with bilateral disease are eligible if they meet other eligibility criteria.

    - Neuropathy: No baseline neuropathy grade > 2

    Exclusion Criteria:

    - Current or anticipated use of other investigational agents

    - Subject has received chemotherapy, radiotherapy or surgery for the treatment of
    breast cancer

    - Subject with metastatic disease

    - History of allergic reactions to compounds of similar chemical or biologic
    composition to carboplatin, docetaxel, doxorubicin, cyclophosphamide, paclitaxel

    - Subjects with inflammatory breast cancer

    - Uncontrolled intercurrent illness including, but not limited to; ongoing or active
    infection, or psychiatric illness/social situations that would limit compliance with
    study requirements

    - Subject is pregnant or nursing

    - Subjects with concomitant or previous malignancies within the last 5 years.
    Exceptions include: adequately treated basal or squamous cell carcinoma of the skin,
    carcinoma in situ of the cervix, and ductal carcinoma in situ (DCIS).

    - Ejection Fraction <50% on ECHO or MUGA

    - Cardiac function: Subjects with congestive heart failure, myocardial infarction,
    unstable angina pectoris, an arterial thrombotic event, stroke or transient ischemia
    attack within the past 12 months, uncontrolled hypertension (Systolic BP>160 or
    Diastolic BP>90), uncontrolled or symptomatic arrhythmia, or grade 2 peripheral
    vascular disease

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 70 Years

    Eligible Gender: Female

    Primary Outcome Measures

    Pathological complete response rates

    Secondary Outcome Measures

    Minimal residual disease rates

    Trial Keywords

    TNBC, breast cancer, neoadjuvant, carboplatin, docetaxel, paclitaxel, doxorubicin, cyclophosphamide