Clinical Trials /

Phase II Breast Ca Carboplatin + Paclitaxel With Pertuzumab + Trastuzumab or Bevacizumab

NCT02436993

Description:

The purpose of this phase II is to study the efficacy and toxicity of carboplatin and paclitaxel with pertuzumab and trastuzumab in HER2 positive and carboplatin and paclitaxel with bevacizumab in HER2 negative in the neoadjuvant setting for the treatment of breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-disease">Breast Cancer</span> Treatment Using Weekly <span class="go-doc-concept go-doc-intervention">Carboplatin</span> + <span class="go-doc-concept go-doc-intervention">Paclitaxel</span> With <span class="go-doc-concept go-doc-intervention">Pertuzumab</span> + <span class="go-doc-concept go-doc-intervention">Trastuzumab</span> (<span class="go-doc-concept go-doc-biomarker">HER2</span>+) or <span class="go-doc-concept go-doc-intervention">Bevacizumab</span> (<span class="go-doc-concept go-doc-biomarker">HER2</span>-) in the Neoadjuvant Setting

Title

  • Brief Title: Breast Cancer Treatment Using Weekly Carboplatin + Paclitaxel With Pertuzumab + Trastuzumab (HER2+) or Bevacizumab (HER2-) in the Neoadjuvant Setting
  • Official Title: A Phase II Study of Breast Cancer Treatment Using Weekly Carboplatin + Paclitaxel With Pertuzumab + Trastuzumab (HER2+) or Bevacizumab (HER2-) in the Neoadjuvant Setting
  • Clinical Trial IDs

    NCT ID: NCT02436993

    ORG ID: UCI 14-67

    NCI ID: 2015-1888

    Trial Conditions

    Breast Carcinoma

    Trial Interventions

    Drug Synonyms Arms
    Carboplatin Paraplatin Carboplatin+Paclitaxel+Bevacizumab (HER2-), Carboplatin+Paclitaxel+Trastuzumab+Pertuzumab (HER2+)
    Paclitaxel Taxol Carboplatin+Paclitaxel+Bevacizumab (HER2-), Carboplatin+Paclitaxel+Trastuzumab+Pertuzumab (HER2+)
    Bevacizumab Avastin Carboplatin+Paclitaxel+Bevacizumab (HER2-)
    Trastuzumab Herceptin Carboplatin+Paclitaxel+Trastuzumab+Pertuzumab (HER2+)
    Pertuzumab Perjeta Carboplatin+Paclitaxel+Trastuzumab+Pertuzumab (HER2+)

    Trial Purpose

    The purpose of this phase II is to study the efficacy and toxicity of carboplatin and
    paclitaxel with pertuzumab and trastuzumab in HER2 positive and carboplatin and paclitaxel
    with bevacizumab in HER2 negative in the neoadjuvant setting for the treatment of breast
    cancer.

    Detailed Description

    OBJECTIVES There are two study components, 1) to evaluate the treatment response and
    toxicity of the protocol, and 2) to investigate the role of Magnetic Resonance Imaging (MRI)
    to monitor and predict the final pathological response.

    Objectives for treatment study component:

    1.1 To estimate 2-year progression-free survival in patients with breast cancer with tumor
    more than 1 cm and/or with clinically detected lymph node treated with neoadjuvant weekly
    Carboplatin and Paclitaxel combined with Trastuzumab + Pertuzumab in HER2-positive disease
    or with Bevacizumab in HER2-negative disease.

    1.2 To measure the microscopic complete pathological response (pCR) rates defined as ypT0 or
    Ductal carcinoma in situ (DCis) tumors in patients treated with this regimen in the
    neoadjuvant setting.

    1.3 To assess complete clinical response (cCR) rates after treatment by physical exam and
    imaging tests (ultrasonography, mammography, or magnetic resonance imaging) clinical
    objective response rate (by Response Evaluation Criteria In Solid Tumors (RECIST)) 1.4 To
    determine the toxicity of this regimen. 1.5 To determine treatment adherence and delivered
    dose intensity of this regimen.

    1.6 To assess the correlation between pCR and cCR. 1.7 To determine the rate of breast
    conservation following neoadjuvant therapy. 1.8 Determine treatment efficacy according to
    subgroups defined according to stage and receptor status.

    Objectives for MRI response monitoring study component:

    1.9 Develop quantitative analysis methods to obtain pre-treatment tumor characteristics in
    breast cancer (including morphological and enhancement kinetic parameters) and select an
    optimal set of features using the logistic regression analysis and the Artificial Neural
    Network (ANN) to predict pathologic complete remission (pCR) in HER2-positive and negative
    arms.

    1.10 Investigate whether the early response patterns in tumor (changes in percent tumor size
    or other tumor characteristic parameters) can be used to predict pathologic complete
    remission (pCR) in HER2 positive and negative arms.

    1.11 Investigate whether combining the pre-treatment characteristic parameters and the early
    response patterns can achieve a higher AUC (area under the Receiver Operating Characteristic
    (ROC) curve) in prediction of pCR than those based on pre-treatment MRI characteristics or
    tumor response patterns alone.

    Trial Arms

    Name Type Description Interventions
    Carboplatin+Paclitaxel+Bevacizumab (HER2-) Experimental Carboplatin weekly 12 doses Paclitaxel weekly 12 doses Bevacizumab every other week, 5 doses Carboplatin, Paclitaxel, Bevacizumab
    Carboplatin+Paclitaxel+Trastuzumab+Pertuzumab (HER2+) Experimental Carboplatin weekly 12 doses Paclitaxel weekly 12 doses Trastuzumab weekly 12 doses Pertuzumab every 3 weeks, 4 doses Carboplatin, Paclitaxel, Trastuzumab, Pertuzumab

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically proven unilateral or bilateral primary breast carcinoma. (In case of
    bilateral cancer, the investigator has to decide prospectively which side will be
    evaluated for the primary endpoint.)

    - Tumor size is clinically at least 1 cm in greatest diameter (palpable or by imaging)
    and/or with involved lymph node. In case of inflammatory disease, the extent of
    inflammation may be the measurable lesion.

    - Documentation of inflammatory breast cancer Inflammatory breast cancer?

    - Woman age > or = 18

    - Performance status of 0-2 by Eastern Cooperative Oncology Group (ECOG) criteria

    - Known HER2 status

    - Normal cardiac function must be documented within 90 days prior to registration.
    Result of ejection fraction must be above the normal limit of the institution.

    - Date of Echo or multigated acquisition (MUGA) (within 90 days)

    - Staging work-up prior to registration

    - Date of physical examination (within 90 days)

    - Date of bilateral mammogram (within 90 days)

    - Date of breast ultrasound (within 30 days)

    - Date of MRI breast (within 30 days)

    - Chest X-ray (within 90 days)

    - Other tests as clinically indicated

    - Laboratory requirements:

    - Hematology:

    - Absolute Neutrophil Count (ANC) 1,500/l

    - Platelets 100,000/l

    - Hepatic Function

    - Total Bilirubin <1x upper limit of normal (ULN)

    - aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 2x ULN

    - Renal Function

    - Creatinine <1.5x ULN

    - Proteinuria

    - Urine dipstick for proteinuria <2+. Patients discovered to have 2+ proteinuria on
    dipstick should undergo a 24-hour urine collection and demonstrate 1g of protein in
    24 hours.

    - Negative pregnancy test for women of childbearing potential within 14 days prior to
    registration.

    - All patients must be informed of the investigational nature of this study and must
    sign and\give written informed consent in accordance with institutional and federal
    guidelines.

    Exclusion Criteria:

    - Evidence of distant metastasis

    - Known or suspected congestive heart failure, angina pectoris requiring antianginal
    medication, or other clinically significant cardiac condition.

    - Pregnant or nursing women may not participate due to the possibility of harm to fetus
    or nursing infants from this treatment regimen. Women of childbearing potential may
    not participate unless they have agreed to use an adequate contraceptive method
    throughout study treatment and for one month after completion of treatment.

    - Male patients

    - Pre-existing peripheral neuropathy of severity grade 2 (limiting instrumental
    activities of daily living).

    - Incomplete wound healing.

    - Active and significant bleeding

    - Known allergy, hypersensitivity or prior infusion reaction to one or more of the
    therapies incorporated into this treatment protocol.

    - Bone marrow depression or hematologic parameters in the range that would increase the
    risk for severe bleeding.

    Exclusion criteria for participating in MRI monitoring sub-study: Subjects will not be
    eligible to participate in the MRI response monitoring sub-study, if they have:

    - Implanted prosthetic heart valves, pacemaker, neuro-stimulation devices, surgical
    clips (hemostatic clips) or other metallic implants.

    - Engaged in occupations or activities which may cause accidental lodging of
    ferromagnetic materials, or have imbedded metal fragments from military activities.

    - Received orthodontic work involving ferromagnetic materials.

    - Claustrophobia (a fear of enclosed spaces).

    - Previously had an allergic response to MR contrast agents (gadolinium).

    - Known history of severe renal insufficiency, asthma, allergic conditions, sickle cell
    anemia, chronic hemolytic anemia, and gastrointestinal disorders.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    2-year progression free survival in patients treated with weekly carboplatin and paclitaxel combined with either trastuzumab and pertuzumab for HER2-positive patients or bevacizumab for HER2-negative patients in the neoadjuvant setting

    Secondary Outcome Measures

    Clinical complete response rates

    Pathologic complete response rates

    Number of toxicities in Carboplatin+Paclitaxel+Bevacizumab (HER2) arm

    Number of toxicities in Carboplatin+Paclitaxel+Trastuzumab+Pertuzumab (HER2+)

    Trial Keywords

    Neoadjuvant Treatment

    Carboplatin

    Paclitaxel

    Pertuzumab

    Trastuzumab

    Bevacizumab