Clinical Trials /

Carboplatin+Nab-paclitaxel, Plus Trastuzumab (HER2+) or Bevacizumab (HER2-) in the Neoadjuvant Setting

NCT00618657

Description:

This phase II is studying the side effects and how well carboplatin and paclitaxel albumin-stabilized nanoparticle formulation when together with bevacizumab or trastuzumab before surgery works in treating patients with stage I-III 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. Monoclonal antibodies, such as bevacizumab and trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving more than one drug (combination chemotherapy) and monoclonal antibody therapy together 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

Title

  • Brief Title: Carboplatin+Nab-paclitaxel, Plus Trastuzumab (HER2+) or Bevacizumab (HER2-) in the Neoadjuvant Setting
  • Official Title: A Phase II Study of Breast Cancer Treatment Using Weekly Carboplatin+Nab-paclitaxel, Plus Trastuzumab (HER2+) or Bevacizumab (HER2-) in the Neoadjuvant Setting

Clinical Trial IDs

  • ORG STUDY ID: UCI 07-61
  • SECONDARY ID: 2007-6084
  • SECONDARY ID: NCI-2010-00155
  • SECONDARY ID: R01CA127927
  • NCT ID: NCT00618657

Conditions

  • Breast Cancer
  • HER2-negative Breast Cancer
  • HER2-positive Breast Cancer
  • Recurrent Breast Cancer
  • Stage IA Breast Cancer
  • Stage IB Breast Cancer
  • Stage II Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer

Interventions

DrugSynonymsArms
CarboplatinCarboplatin Hexal, Carboplatino, CBDCAArm I (HER-2 positive)
paclitaxel albumin-stabilized nanoparticle formulationAlbumin-Stabilized Nanoparticle Paclitaxel, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxel, Nanoparticle PaclitaxelArm I (HER-2 positive)
bevacizumabanti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, anti-VEGF rhuMAb, recombinant humanized anti-VEGF monoclonal antibody, rhuMAb VEGFArm II (HER-2 negative)
trastuzumabanti-c-erB-2, MOAB HER2, monoclonal antibody c-erb-2, monoclonal antibody HER2, rhuMAb HER2Arm I (HER-2 positive)

Purpose

This phase II is studying the side effects and how well carboplatin and paclitaxel albumin-stabilized nanoparticle formulation when together with bevacizumab or trastuzumab before surgery works in treating patients with stage I-III 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. Monoclonal antibodies, such as bevacizumab and trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving more than one drug (combination chemotherapy) and monoclonal antibody therapy together 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 estimate 2 year progression-free survival in patients with breast cancer more than 1 cm
      and/or lymph node positive breast cancer treated with weekly Carboplatin/Nab-Paclitaxel (with
      trastuzumab in patients with HER2+ disease, and with bevacizumab in HER2-).

      II. To measure clinical response rates in patients treated in the neoadjuvant setting.

      III. To measure the microscopic pathological response rate of this regimen in patients
      treated in the neoadjuvant setting.

      IV. To measure the toxicity and delivered dose intensity of this regimen. V. To assess the
      association between microscopic pathologic complete response and clinical complete response
      at the primary tumor site in these patients.

      VI. To measure the outcome of patients treated with doxorubicin and cyclophosphamide with
      patients not treated with doxorubicin and cyclophosphamide.

      SECONDARY OBJECTIVES:

      I. Develop quantitative analysis methods to obtain pre-treatment tumor characteristic
      morphological, enhancement kinetic, and Choline metabolic parameters in breast cancer. Select
      an optimal set of features using the logistic regression analysis and the Artificial Neural
      Network (ANN) to predict pathologic complete remission (pCR) in HER-2 positive and negative
      arm.

      II. Investigate whether the early response patterns, analyzed using the percent tumor size
      changes, or changes in other lesion characteristic parameters, can be used to predict
      pathologic complete remission (pCR) in HER-2 positive and negative arm.

      III. Investigate whether combining the pre-treatment tumor characteristic parameters, and the
      early response pattern during the treatment course, can achieve a higher "area under the
      receiver operating characteristic (ROC) curve" (AUC) in prediction of pCR than those based on
      pre-treatment MRI characteristics or tumor response patterns alone.

      OUTLINE: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30
      minutes and carboplatin IV over 60 minutes once weekly for 12 weeks. Patients with
      HER2-positive disease receive trastuzumab IV over 30-90 minutes once weekly for 12 weeks and
      patients with HER2-negative disease receive bevacizumab IV over 30-90 minutes once every two
      weeks for 5 doses. Treatment continues in the absence of disease progression or unacceptable
      toxicity. Beginning 21-40 days later, patients undergo surgery.

      After completion of study treatment, patients are followed for 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (HER-2 positive)ExperimentalPatients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes, carboplatin IV over 60 minutes, and trastuzumab IV over 90 minutes , then weekly over 30-60 minutes. Treatment repeats every week for 12 weeks in the absence of disease progression or unacceptable toxicity. In both arms, beginning 21-40 days later, patients undergo surgery.
  • Carboplatin
  • paclitaxel albumin-stabilized nanoparticle formulation
  • trastuzumab
Arm II (HER-2 negative)ExperimentalPatients receive paclitaxel albumin-stabilized nanoparticle formulation and carboplatin as in Arm I. Patients also receive bevacizumab IV over 90 or 60 or 30 minutes once every two weeks for 5 doses in the absence of disease progression or unacceptable toxicity. In both arms, beginning 21-40 days later, patients undergo surgery.
  • Carboplatin
  • paclitaxel albumin-stabilized nanoparticle formulation
  • bevacizumab

Eligibility Criteria

        -  Patients must be women with a histologically confirmed diagnosis of breast cancer that
             is more than 1 cm and or lymph node positive

          -  Physical examination, and scans needed for tumor assessment must be performed within
             90 days prior to registration

          -  Patients with the clinical diagnosis of congestive heart failure or angina pectoris
             are NOT eligible

          -  Serum creatinine within normal limits within 90 days prior to registration

          -  Bilirubin within normal limits within 90 days prior to registration

          -  Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate
             transaminase (SGPT) =< 2 x the institutional upper limit of normal within 90 days
             prior to registration

          -  Absolute neutrophil count (ANC) of >= 1,500/microliters within 90 days prior to
             registration

          -  Platelet count of >= 100,000/microliters within 90 days prior to registration

          -  Patients must have a performance status of 0-2 by Zubrod criteria

          -  Pregnant or nursing women may not participate; women of reproductive potential may not
             participate unless they have agreed to use an effective contraceptive method;
             pregnancy test required for women of childbearing potential

          -  In calculating days of tests and measurements, the day a test or measurement is done
             is considered day 0; therefore, if a test is done on a Monday, the Monday four weeks
             later would be considered day 28; this allows for efficient patient scheduling without
             exceeding the guidelines; if day 28 or 42 falls on a weekend or holiday, the limit may
             be extended to the next working day

          -  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
      
Maximum Eligible Age:90 Years
Minimum Eligible Age:21 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival
Time Frame:2 years
Safety Issue:
Description:Progression is defined as a new lesion or a greater than or equal to 25% increase in the product of the largest perpendicular diameters of any one lesion on clinical exam or by ultrasound (U/S) or MRI. Analyzed using the Kaplan-Meier method. Cox proportional-hazards analysis will be used to derive the hazard ratio and 95% confidence interval between the two treatment arms, adjusted for clinical and demographic variables.

Secondary Outcome Measures

Measure:Clinical complete response in the neoadjuvant setting
Time Frame:Up to 5 years
Safety Issue:
Description:Defined as normal breast on physical exam. No mass, no thickening, no erythema, no peau d'orange. The 95% confidence interval (CI) will be computed.
Measure:Microscopic pCR in the neoadjuvant setting
Time Frame:Up to 5 years
Safety Issue:
Description:Defined as no evidence of microscopic invasive tumor at the primary tumor site in the surgical specimen. The 95% CI will be computed.
Measure:Toxicity of the combinations in HER2 positive and HER2 negative breast cancer assessed using the National Cancer Institute (NCI) Common Toxicity Criteria version 3.0
Time Frame:Up to 5 years
Safety Issue:
Description:The frequency of toxicities will be recorded.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:University of California, Irvine

Trial Keywords

  • pre-operative
  • neo-adjuvant
  • triple negative
  • HER2 positive
  • hormone receptor positive
  • breast
  • Carboplatin
  • Nab-paclitaxel
  • Trastuzumab
  • Bevacizumab
  • Inflammatory

Last Updated

January 11, 2018