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

NCT ID: NCT00618657

Last Updated: 2024-02-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2021-07-31

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.

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Carboplatin

Intervention Type: DRUG

Given IV

paclitaxel albumin-stabilized nanoparticle formulation

Intervention Type: DRUG

Given IV

trastuzumab

Intervention Type: DRUG

Given IV

magnetic resonance imaging

Intervention Type: PROCEDURE

Optional correlative studies

therapeutic conventional surgery

Intervention Type: PROCEDURE

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

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.

Group Type: EXPERIMENTAL

Carboplatin

Intervention Type: DRUG

Given IV

paclitaxel albumin-stabilized nanoparticle formulation

Intervention Type: DRUG

Given IV

bevacizumab

Intervention Type: DRUG

Given IV

magnetic resonance imaging

Intervention Type: PROCEDURE

Optional correlative studies

therapeutic conventional surgery

Intervention Type: PROCEDURE

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

Interventions

Carboplatin

Given IV

Intervention Type: DRUG

paclitaxel albumin-stabilized nanoparticle formulation

Given IV

Intervention Type: DRUG

bevacizumab

Given IV

Intervention Type: DRUG

trastuzumab

Given IV

Intervention Type: DRUG

magnetic resonance imaging

Optional correlative studies

Intervention Type: 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

Intervention Type: PROCEDURE

Other Intervention Names

Carboplatin Hexal; Carboplatino; CBDCA; Albumin-Stabilized Nanoparticle Paclitaxel; nab paclitaxel; nab-paclitaxel; nanoparticle albumin-bound paclitaxel; Nanoparticle Paclitaxel; anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; anti-VEGF rhuMAb; recombinant humanized anti-VEGF monoclonal antibody; rhuMAb VEGF; anti-c-erB-2; MOAB HER2; monoclonal antibody c-erb-2; monoclonal antibody HER2; rhuMAb HER2; MRI; NMR imaging; NMRI; nuclear magnetic resonance imaging

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of California, Irvine

OTHER

Sponsor Role: lead

Responsible Party

Rita Sanghvi, Mehta

HS Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rita Mehta, M.D.

Role: PRINCIPAL_INVESTIGATOR

Chao Family Comprehensive Cancer Center

Locations

Chao Family Comprehensive Cancer Center

Orange, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

UCI 07-61

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2010-00155

Identifier Type: OTHER

Identifier Source: secondary_id

R01CA127927

Identifier Type: NIH

Identifier Source: secondary_id

View Link

20076084

Identifier Type: -

Identifier Source: org_study_id