Sunitinib Malate, Paclitaxel, Doxorubicin Hydrochloride, and Cyclophosphamide Before Surgery in Treating Patients With Stage IIB-IIIC Breast Cancer

NCT00513695 | Completed Phase 2 Results

• 2 other identifiers: 6488NCI-2010-00607
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 7

Brief Summary

This phase II trial studies how well giving sunitinib malate together with paclitaxel, doxorubicin hydrochloride, and cyclophosphamide before surgery works in treating patients with stage IIB-IIIC breast cancer. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel, doxorubicin hydrochloride, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sunitinib malate together with combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed

Conditions

Inflammatory Breast Cancer; Male Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Microscopic Pathologic CR (pCR) Rate

  Defined as no evidence of microscopic invasive tumor present at primary tumor site in the surgical specimen and calculated with exact 90% binomial confidence interval.

  At the time of surgery

Secondary Outcomes (5)

• Clinical Complete Response and Correlation With Plasma VEGF, Soluble VCAM (sVCAM), and Circulating Endothelial Cells (CECs) Levels

  At baseline, after week 12 of therapy, and prior to surgery

• Relapse Rate

  Up to two years

• Time to Disease Progression

  Up to 2 years

• Overall Survival

  Up to 2 years

• Number and Percent of Subjects Reporting Adverse Events

  28 days after the last dose of study drug

Study Arms (1)

Treatment (neoadjuvant chemotherapy before surgery)

EXPERIMENTAL

Patients receive neoadjuvant chemotherapy comprising sunitinib malate PO once daily and paclitaxel IV over 1 hour once weekly for 8-12 weeks in the absence of disease progression or unacceptable toxicity. Beginning within 3 weeks of completion of sunitinib malate and paclitaxel, patients receive doxorubicin IV once weekly for 15 weeks, cyclophosphamide PO once daily for 15 weeks, and filgrastim SC on days 2-7 for 16 weeks in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo surgery.

Drug: sunitinib malate; Drug: paclitaxel; Drug: doxorubicin hydrochloride; Drug: cyclophosphamide; Biological: filgrastim; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis; Other: flow cytometry

Interventions

sunitinib malate DRUG

Given PO

Also known as: SU11248, sunitinib, Sutent

Treatment (neoadjuvant chemotherapy before surgery)

paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, TAX, Taxol

Treatment (neoadjuvant chemotherapy before surgery)

doxorubicin hydrochloride DRUG

Given IV

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

Treatment (neoadjuvant chemotherapy before surgery)

cyclophosphamide DRUG

Given PO

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

Treatment (neoadjuvant chemotherapy before surgery)

filgrastim BIOLOGICAL

Given SC

Also known as: G-CSF, Neupogen

Treatment (neoadjuvant chemotherapy before surgery)

therapeutic conventional surgery PROCEDURE

Undergo surgery

Treatment (neoadjuvant chemotherapy before surgery)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (neoadjuvant chemotherapy before surgery)

flow cytometry OTHER

Correlative studies

Treatment (neoadjuvant chemotherapy before surgery)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Be informed of the investigational nature of the study and all pertinent aspects of the trial and must sign and give written consent in accordance with institutional and federal guidelines
• Have a histologically-confirmed diagnosis of breast cancer that is locally advanced or inflammatory; inflammatory breast cancer is defined as erythema and peau d'orange involving half or more of the breast with a histologic diagnosis of breast cancer; the finding of focal dermal lymphatic involvement on histology does not constitute inflammatory breast cancer
• Have selected stage IIB (T3, N0, M0) or IIIA (T3, N1-2, M0 or T0-2, N2, M0) disease judged primarily unresectable by an experienced breast surgeon or otherwise deemed appropriate candidates for neoadjuvant treatment or stage IIIB (T4, any N, M0) or stage IIIC (any T, N3, M0) disease
• Patients must have a performance status of 0-2 by Zubrod criteria
• Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3
• Platelet count \>= 100,000 cells/mm\^3
• Serum creatinine =\< 1.5 x institutional upper limit of normal (IULN)
• Bilirubin =\< 2.0
• Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT)/alkaline phosphatase =\< 2.0 x IULN
• Have a multi gated acquisition scan (MUGA) or echocardiogram scan performed within 3 months prior to enrollment and have a left ventricular ejection fraction (LVEF) % greater than the institutional lower limit of normal
• Be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures

You may not qualify if:

• Have evidence of distant metastases
• Have tumors that overexpress human epidermal growth factor receptor 2 (HER2)/neu as evidenced by 3+ staining by immunohistochemistry or gene amplification by fluorescent in situ hybridization (FISH)
• Have received any prior chemotherapy or hormonal therapy for breast cancer
• Have received prior radiation therapy or prior definitive surgery for breast cancer
• Have a clinical diagnosis of congestive heart failure or angina pectoris or any of the following within the 6 months prior to study drug administration:, myocardial infarction, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
• Have ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0 grade \>= 2
• Have uncontrolled hypertension (\>150/100 mm Hg despite optimal medical therapy)
• Have pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
• Have a known, active infection
• Have any prior malignancy except for adequately treated basal cell or squamous cell skin cancer, any in situ cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission or any other cancer from which the patient has been disease-free for 5 years
• Human immunodeficiency virus (HIV) positive
• Are receiving or planning to receive any concurrent anticancer therapy while receiving protocol treatment
• Are receiving or planning to receive concurrent treatment on another clinical trial (supportive care trials or non-treatment trials, e.g. quality of life (QOL) are allowed; participation in the companion imaging trial, dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) and fludeoxyglucose F 18 positron emission tomography (FDG PET) with Kinetic Analysis to Monitor Breast Cancer Response to Neoadjuvant Sunitinib and Metronomic Chemotherapy is also allowed)
• Be pregnant or breast feeding; female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy; all female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment; male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy; the definition of effective contraception will be based on the judgment of the principal investigator or a designated associate
• Have other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study

Sponsors & Collaborators

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

Study Sites (7)

Anchorage Oncology Centre

Anchorage, Alaska, 99508, United States

Location

Katmai Oncology Group

Anchorage, Alaska, 99508, United States

Location

Arizona Cancer Center

Tucson, Arizona, 85724-5024, United States

Location

Saint Luke's Mountain States Tumor Institute

Boise, Idaho, 83712, United States

Location

Skagit Valley Hospital

Mount Vernon, Washington, 98273, United States

Location

Olympic Medical Center

Port Angeles, Washington, 98362, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Inflammatory Breast Neoplasms; Breast Neoplasms, Male; Breast Neoplasms

Interventions

Sunitinib; Paclitaxel; Taxes; Doxorubicin; Cyclophosphamide; Filgrastim; Granulocyte Colony-Stimulating Factor; Flow Cytometry

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; 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; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Jennifer Specht, MD
• Organization: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

jspecht@uw.edu

(206) 288-6889

Study Officials

• Jennifer Specht

  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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 8, 2007
• First Posted: August 9, 2007
• Study Start: June 1, 2007
• Primary Completion: August 1, 2012
• Study Completion: October 16, 2017
• Last Updated: August 7, 2019
• Results First Posted: May 10, 2017

Record last verified: 2019-07

Locations

US (7)