Combination Chemotherapy and Filgrastim Before Surgery in Treating Patients With HER2-Positive Breast Cancer That Can Be Removed By Surgery

NCT00194779 | Completed Phase 2 Results

• 2 other identifiers: 6278NCI-2011-00934
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well giving combination chemotherapy and filgrastim together before surgery works in treating patients with human epidermal growth receptor 2 (HER2)-positive breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, and paclitaxel work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. 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. Giving doxorubicin hydrochloride, cyclophosphamide, and filgrastim together followed by paclitaxel before surgery may be an effective treatment for breast cancer

Conditions

Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-positive Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Combined Rate of Microscopic pCR and Macroscopic Pathologic Complete Response (mCR)

  Microscopic pCR: No evidence of microscopic invasive tumor at the primary site or in the regional lymph nodes at the time of definitive surgical resection. mCR: The examining pathologist cannot identify gross residual tumor mass in the surgical specimen. This differs from a pCR where the specimen must also be negative for invasive tumor by microscopy. For this study, we are using a definition of mCR that will make the trial more translatable to other institutions. For this study, mCR will be defined as no focus of invasive cancer \>= 1 cm. Count of participants with either a pCR or mCR.

  Up to 16 weeks

Secondary Outcomes (8)

• Number and Percent of Patients Reporting Grade 2, 3, 4, or Fatal Toxicities of These Regimens, Need for Dose Reduction, or Treatment Interruption or Discontinuation

  From the initiation of study treatments to 30 days after the end of neoadjuvant treatment or adjuvant treatment if received

• Correlation of Molecular Markers With Response

  After completion of neoadjuvant therapy

• Relapse Rate in Patients With Operable Breast Cancer Treated With Neoadjuvant Chemotherapy for 12 Weeks Followed by Weekly Paclitaxel for 12 Weeks and Adjuvant Chemotherapy

  Up to 8 years

• Time to Progression

  Up to 5 years

• OS in Patients With Operable Breast Cancer Treated With Neoadjuvant Chemotherapy for 12 Weeks Followed Weekly Paclitaxel for 12 Weeks and Adjuvant Chemotherapy With XMN

  1, 2, and 5 years

Study Arms (1)

Treatment (neoadjuvant therapy, adjuvant therapy)

EXPERIMENTAL

See Detailed Description.

Drug: doxorubicin hydrochloride; Drug: cyclophosphamide; Drug: paclitaxel; Biological: filgrastim; Drug: capecitabine; Drug: methotrexate; Drug: vinorelbine tartrate; Procedure: needle biopsy; Procedure: therapeutic conventional surgery; Other: immunohistochemistry staining method; Biological: trastuzumab; Drug: tamoxifen citrate; Drug: letrozole; Other: laboratory biomarker analysis

Interventions

doxorubicin hydrochloride DRUG

Given IV

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

Treatment (neoadjuvant therapy, adjuvant therapy)

cyclophosphamide DRUG

Given PO

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

Treatment (neoadjuvant therapy, adjuvant therapy)

paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, TAX, Taxol

Treatment (neoadjuvant therapy, adjuvant therapy)

filgrastim BIOLOGICAL

Given SC

Also known as: G-CSF, Neupogen

Treatment (neoadjuvant therapy, adjuvant therapy)

capecitabine DRUG

Given PO

Also known as: CAPE, Ro 09-1978/000, Xeloda

Treatment (neoadjuvant therapy, adjuvant therapy)

methotrexate DRUG

Given IV

Also known as: amethopterin, Folex, methylaminopterin, Mexate, MTX

Treatment (neoadjuvant therapy, adjuvant therapy)

vinorelbine tartrate DRUG

Given IV

Also known as: Eunades, navelbine ditartrate, NVB, VNB

Treatment (neoadjuvant therapy, adjuvant therapy)

needle biopsy PROCEDURE

Correlative studies

Also known as: aspiration biopsy, puncture biopsy

Treatment (neoadjuvant therapy, adjuvant therapy)

therapeutic conventional surgery PROCEDURE

Undergo definitive breast surgery

Treatment (neoadjuvant therapy, adjuvant therapy)

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Treatment (neoadjuvant therapy, adjuvant therapy)

trastuzumab BIOLOGICAL

Given IV

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

Treatment (neoadjuvant therapy, adjuvant therapy)

tamoxifen citrate DRUG

Given PO

Also known as: Nolvadex, TAM, tamoxifen, TMX

Treatment (neoadjuvant therapy, adjuvant therapy)

letrozole DRUG

Given PO

Also known as: CGS 20267, Femara, LTZ

Treatment (neoadjuvant therapy, adjuvant therapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (neoadjuvant therapy, adjuvant therapy)

Eligibility Criteria

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

You may qualify if:

• Have known tumor HER-2/neu expression; if determination is "intermediate" by immunohistochemistry, fluorescent in situ hybridization (FISH) must be performed; protocol therapy is determined by HER-2/neu result
• Have histologically confirmed, operable breast cancer that is either:
• Hormone receptor (estrogen receptor \[ER\] or progesterone receptor \[PR\]) positive and HER2/neu positive or
• ER/PR negative
• Have radiographically measurable breast cancer \> 1cm (Operable lesions are T1c-T3 and N0-N2a; histologic confirmation should be by core needle biopsy only)
• Be chemotherapy naïve
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Absolute neutrophil count (ANC) \>= 1,500
• Platelet count \>= 100,000
• Serum creatinine =\< 1.5 x international upper limit of normal (IULN)
• Bilirubin \< 2.0
• Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvate transaminase (SGPT) =\< 2 x IULN
• Alkaline phosphatase =\< 2 x IULN
• Have staging studies and tumor assessment prior to registration; staging studies include physical exam with bidimensional tumor measurements and mammography, ultrasound, or magnetic resonance imaging (MRI) to assess tumor volume; sentinel lymph node dissection or axillary needle biopsy must be completed prior to enrollment; MRI and positron emission tomography (PET) (fluorodeoxyglucose \[FDG\], methoxyisobutylisonitrile \[MIBI\] and fluoroestradiol \[FES\]) imaging will be done before enrollment if clinically indicated to assess tumor volume or may be done within the first month of study participation on another institutional protocol
• 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 multi gated acquisition scan (MUGA) prior to enrollment; patients with breast cancer that is HER-2/neu positive who will receive herceptin (trastuzumab) must have an echocardiogram or MUGA scan; the left ventricular ejection fraction (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

You may not qualify if:

• Primary tumor =\< 1 cm, not measurable; inflammatory disease
• Pregnant or lactating; woman of childbearing potential with either a positive or no pregnancy test at baseline are excluded; postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential; patients must agree to continue contraception for 30 days from the date of the last study drug administration; woman of childbearing potential not using a reliable and appropriate contraceptive method are excluded
• Evidence of distant metastatic disease
• Prior chemotherapy or hormonal therapy for breast cancer
• 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 situ cervical cancer or other stage I or II cancer from which the patient has been disease free for at least 5 years
• Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil
• Previous enrollment in an investigational drug study within the past four weeks
• History of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance with oral drug intake
• Patients with cardiac disease that would preclude the use of Adriamycin, Taxol or Herceptin are not eligible
• Active cardiac disease:
• 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

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; Paclitaxel; Taxes; Filgrastim; Granulocyte Colony-Stimulating Factor; Capecitabine; Methotrexate; merphos; Vinorelbine; Biopsy, Needle; Immunohistochemistry; Trastuzumab; Tamoxifen; Letrozole

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; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Punctures; Investigative Techniques; Histocytochemistry; Histological Techniques; Immunologic Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Nitriles; Triazoles; Azoles

Results Point of Contact

• Title: Dr. Hannah Linden
• Organization: University of Washington / Seattle Cancer Care Alliance

hmlinden@uw.edu

206-288-6989

Study Officials

• Georgiana Ellis

  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: September 13, 2005
• First Posted: September 19, 2005
• Study Start: October 1, 2003
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2011
• Last Updated: March 12, 2018
• Results First Posted: March 12, 2018

Record last verified: 2018-02

Locations

US (1)