Doxorubicin Hydrochloride, Cyclophosphamide, and Filgrastim Followed By Paclitaxel Albumin-Stabilized Nanoparticle Formulation With or Without Trastuzumab in Treating Patients With Breast Cancer Previously Treated With Surgery

NCT00407888 | Completed Phase 2 Results

• 2 other identifiers: 6141NCI-2010-02117
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, 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. Colony-stimulating factors, such as filgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Monoclonal antibodies, such as 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 combination chemotherapy and filgrastim together with trastuzumab may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving doxorubicin hydrochloride, cyclophosphamide, and filgrastim together followed by paclitaxel albumin-stabilized nanoparticle formulation and trastuzumab works in treating patients with breast cancer previously treated with surgery

Conditions

Estrogen Receptor-positive Breast Cancer; HER2-positive 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; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival Following a Dose-intensive Weekly Regimen of Adriamycin + Oral Cyclophosphamide Augmented With G-CSF Support Followed by Abraxane and Herceptin

  2 years

Secondary Outcomes (4)

• Delivered Dose Intensity of the Regimen

  After at least one course of Adriamycin, up to 12 weeks.

• Toxicity Associated With This Regimen

  After at least one course of Adriamycin, up to 12 weeks.

• Time to Treatment Failure

  Up to 6 years

• Overall Survival

  Up to 6 years.

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive dose-intensive chemotherapy comprising doxorubicin hydrochloride IV over 10-15 minutes on day 1, oral cyclophosphamide once daily on days 1-7, and filgrastim subcutaneously on days 2-7. Courses repeat every 7 days for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Beginning 1 week later, patients then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once a week for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients with HER-2/neu positive disease also receive trastuzumab IV over 30-90 minutes once a week for 1 year in the absence of disease progression or unacceptable toxicity.

Drug: doxorubicin hydrochloride; Drug: cyclophosphamide; Biological: filgrastim; Drug: paclitaxel albumin-stabilized nanoparticle formulation; Biological: trastuzumab; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment

Interventions

doxorubicin hydrochloride DRUG

Given IV

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF

Arm I

cyclophosphamide DRUG

Given orally

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Arm I

filgrastim BIOLOGICAL

Given SC

Also known as: G-CSF, Neupogen

Arm I

paclitaxel albumin-stabilized nanoparticle formulation DRUG

Given IV

Also known as: ABI-007, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxel

Arm I

trastuzumab BIOLOGICAL

Given IV

Also known as: anti-c-erB-2, Herceptin, MOAB HER2

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

quality-of-life assessment PROCEDURE

Ancillary studies

Also known as: quality of life assessment

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a histologically confirmed diagnosis of primary breast carcinoma that has been surgically resected; (this regimen is not intended for neoadjuvant treatment)
• + nodes
• OR if 1-3 + nodes, either ER OR HER-2/neu+
• OR have high-risk node negative disease that is HER-2/neu positive OR \>= 2.0 cm tumor size
• HER-2/new + definition: patient has known tumor HER-2/new expression = 3+ by IHC or, if 2+ by IHC confirmed to be FISH positive
• Patients with clinically apparent cardiac disease, or history of same, are not eligible; patients who are \>= 60 years of age or who have a history of hypertension must have an echocardiogram or MUGA prior to enrollment; patients with breast cancer that is HER-2/neu positive and a treatment plan that includes Herceptin must have an echocardiogram or MUGA scan prior to enrollment; the LVEF must be within the institutional normal range; if LVEF is \> 75%, the investigator should consider having the LVEF reviewed or repeating the MUGA prior to registration
• WBC \>= 4,000
• ANC \>= 1,500
• Platelet count \>= 100,000
• Serum creatinine =\< 1.5 x IULN
• Bilirubin =\< 2.0
• SGOT/SGPT/alkaline phosphatase =\< 2 x IULN
• Elevations greater than these require metastatic work up
• Be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study specific screening procedures

You may not qualify if:

• Except for the following, no other malignancy is allowed: synchronous ipsilateral breast cancer of the same subtype (ER/PR, HER-2/neu), adequately treated basal cell or squamous cell skin cancer, in situcervical cancer or other stage I or II cancer from which the patient has been disease free for at least 5 years
• Patients with cardiac disease that would preclude the use of Adriamycin, Taxol or Herceptin are not eligible; this includes:
• Angina pectoris that requires the use of antianginal medication
• Cardiac arrhythmia requiring medication
• Severe conduction abnormality
• Clinically significant valvular disease
• Cardiomegaly on chest x-ray
• Ventricular hypertrophy on EKG
• Uncontrolled hypertension, (diastolic greater than 100 mm/Hg or systolic \> 200 mm/hg)
• Current use of digitalis or beta blockers for CHF
• Clinically significant pericardial effusion
• Myocardial infarction documented as a clinical diagnosis or by EKG or any other test
• Documented congestive heart failure
• Documented cardiomyopathy
• Documented arrhythmia or cardiac valvular disease that requires medication or is medically significant

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Cyclophosphamide; Filgrastim; Granulocyte Colony-Stimulating Factor; Taxes; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Albumins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Hannah Linden MD FACP
• Organization: Medical Oncology University of Washington

hmlinden@uw.edu

206-288-6989

Study Officials

• Vijayakrishna K Gadi, MDPHD

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigator

Study Record Dates

• First Submitted: December 4, 2006
• First Posted: December 5, 2006
• Study Start: May 1, 2006
• Primary Completion: May 1, 2009
• Study Completion: July 1, 2012
• Last Updated: August 31, 2017
• Results First Posted: August 31, 2017

Record last verified: 2017-08

Locations

US (1)