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

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ClinicalTrials.gov Identifier: NCT00618657
Recruitment Status : Active, not recruiting
First Posted : February 20, 2008
Last Update Posted : January 16, 2018
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Rita Sanghvi, Mehta, University of California, Irvine

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Drug: Carboplatin Drug: paclitaxel albumin-stabilized nanoparticle formulation Drug: bevacizumab Drug: trastuzumab Procedure: magnetic resonance imaging Procedure: therapeutic conventional surgery Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 132 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : February 2008
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm I (HER-2 positive)
Patients 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.
Drug: Carboplatin
Given IV
Other Names:
  • Carboplatin Hexal
  • Carboplatino
  • CBDCA

Drug: paclitaxel albumin-stabilized nanoparticle formulation
Given IV
Other Names:
  • Albumin-Stabilized Nanoparticle Paclitaxel
  • nab paclitaxel
  • nab-paclitaxel
  • nanoparticle albumin-bound paclitaxel
  • Nanoparticle Paclitaxel

Drug: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • MOAB HER2
  • monoclonal antibody c-erb-2
  • monoclonal antibody HER2
  • rhuMAb HER2

Procedure: magnetic resonance imaging
Optional correlative studies
Other Names:
  • MRI
  • NMR imaging
  • NMRI
  • nuclear magnetic resonance imaging

Procedure: therapeutic conventional surgery
Post-chemotherapy surgery for patients with a response or stable disease must take place no sooner than 21 days after last dose of Herceptin; and 40 days after last dose of bevacizumab to allow for normalization of blood counts

Experimental: Arm II (HER-2 negative)
Patients 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.
Drug: Carboplatin
Given IV
Other Names:
  • Carboplatin Hexal
  • Carboplatino
  • CBDCA

Drug: paclitaxel albumin-stabilized nanoparticle formulation
Given IV
Other Names:
  • Albumin-Stabilized Nanoparticle Paclitaxel
  • nab paclitaxel
  • nab-paclitaxel
  • nanoparticle albumin-bound paclitaxel
  • Nanoparticle Paclitaxel

Drug: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • anti-VEGF rhuMAb
  • recombinant humanized anti-VEGF monoclonal antibody
  • rhuMAb VEGF

Procedure: magnetic resonance imaging
Optional correlative studies
Other Names:
  • MRI
  • NMR imaging
  • NMRI
  • nuclear magnetic resonance imaging

Procedure: therapeutic conventional surgery
Post-chemotherapy surgery for patients with a response or stable disease must take place no sooner than 21 days after last dose of Herceptin; and 40 days after last dose of bevacizumab to allow for normalization of blood counts




Primary Outcome Measures :
  1. Progression free survival [ Time Frame: 2 years ]
    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 :
  1. Clinical complete response in the neoadjuvant setting [ Time Frame: Up to 5 years ]
    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.

  2. Microscopic pCR in the neoadjuvant setting [ Time Frame: Up to 5 years ]
    Defined as no evidence of microscopic invasive tumor at the primary tumor site in the surgical specimen. The 95% CI will be computed.

  3. 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 ]
    The frequency of toxicities will be recorded.



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00618657


Locations
United States, California
Chao Family Comprehensive Cancer Center
Orange, California, United States, 92868
Sponsors and Collaborators
University of California, Irvine
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Investigators
Principal Investigator: Rita Mehta, M.D. Chao Family Comprehensive Cancer Center

Responsible Party: Rita Sanghvi, Mehta, HS Clinical Professor, University of California, Irvine
ClinicalTrials.gov Identifier: NCT00618657     History of Changes
Other Study ID Numbers: UCI 07-61
2007-6084 ( Other Identifier: University of California, Irvine )
NCI-2010-00155 ( Other Identifier: NCI Clinical Trials Reporting Program (CTRP) )
R01CA127927 ( U.S. NIH Grant/Contract )
First Posted: February 20, 2008    Key Record Dates
Last Update Posted: January 16, 2018
Last Verified: January 2018

Keywords provided by Rita Sanghvi, Mehta, University of California, Irvine:
breast
Inflammatory
pre-operative
neo-adjuvant
triple negative
HER2 positive
hormone receptor positive
Carboplatin
Nab-paclitaxel
Trastuzumab
Bevacizumab

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Bevacizumab
Carboplatin
Trastuzumab
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immunologic Factors