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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; HER2-positive Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIIC Breast Cancer; Recurrent Breast Cancer; HER2-negative Breast Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: paclitaxel albumin-stabilized nanoparticle formulation; Drug: trastuzumab; Drug: bevacizumab; Procedure: magnetic resonance imaging; Procedure: therapeutic conventional surgery

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
• Enrollment (Actual): 127
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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; Nanoparticle Paclitaxel; nab-paclitaxel; nab paclitaxel; nanoparticle albumin-bound paclitaxel; Drug: trastuzumab; Given IV; Other Names: rhuMAb HER2; anti-c-erB-2; MOAB HER2; monoclonal antibody c-erb-2; monoclonal antibody HER2; Procedure: magnetic resonance imaging; Optional correlative studies; Other Names: MRI; NMRI; nuclear magnetic resonance imaging; NMR 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; Nanoparticle Paclitaxel; nab-paclitaxel; nab paclitaxel; nanoparticle albumin-bound paclitaxel; Drug: bevacizumab; Given IV; Other Names: anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; rhuMAb VEGF; anti-VEGF rhuMAb; recombinant humanized anti-VEGF monoclonal antibody; Procedure: magnetic resonance imaging; Optional correlative studies; Other Names: MRI; NMRI; nuclear magnetic resonance imaging; NMR 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Complete Response in the Neoadjuvant Setting	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.	Up to 5 years
Number of Participants With no Evidence of Microscopic pCR in the Neoadjuvant Setting	Defined as no evidence of microscopic invasive tumor at the primary tumor site in the surgical specimen. The 95% CI will be computed.	Up to 5 years
Number of Participants With 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	The frequency of toxicities will be recorded.	Up to 5 years

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Rita Mehta, M.D., Chao Family Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): July 1, 2021

Study Registration Dates

• First Submitted: February 7, 2008
• First Submitted That Met QC Criteria: February 19, 2008
• First Posted (Estimated): February 20, 2008

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Bevacizumab; breast; Carboplatin; Trastuzumab; hormone receptor positive; Inflammatory; HER2 positive; Nab-paclitaxel; neo-adjuvant; triple negative; pre-operative
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Carboplatin; Paclitaxel; Trastuzumab; Antibodies; Immunoglobulins; Bevacizumab; Albumin-Bound Paclitaxel; Antibodies, Monoclonal; Antineoplastic Agents, Immunological
• Other Study ID Numbers: 20076084; NCI-2010-00155 (Other Identifier: NCI Clinical Trials Reporting Program (CTRP)); R01CA127927 (U.S. NIH Grant/Contract); UCI 07-61 (Other Identifier: CFCCC)