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

NCT ID: NCT00513695

Last Updated: 2019-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2017-10-16

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

Detailed Description

PRIMARY OBJECTIVES:

I.To assess the microscopic pathologic complete response rate (pCR) in patients treated with a two part, neoadjuvant regimen consisting of daily oral sunitinib with weekly IV paclitaxel for 12 weeks followed by weekly doxorubicin and daily oral cyclophosphamide given with filgrastim (G-CSF) support for 15 weeks.

SECONDARY OBJECTIVES:

I. To assess the association between microscopic pCR and clinical complete response rate at the primary tumor site.

II. To assess the relapse rate, overall and disease-free survival in patients with breast cancer treated with neoadjuvant chemotherapy consisting of daily oral sunitinib with weekly IV paclitaxel for 12 weeks followed weekly doxorubicin and daily oral cyclophosphamide given with G-CSF support for 15 weeks.

III. To assess the toxicity associated with these regimens. IV. To explore the relationship between planned correlative laboratory and clinical studies and indicators of efficacy such as pathologic response, clinical response and relapse.

OUTLINE:

Patients receive neoadjuvant chemotherapy comprising sunitinib malate orally (PO) once daily and paclitaxel intravenously (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 subcutaneously (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.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Conditions

Inflammatory Breast Cancer; Male 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: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (neoadjuvant chemotherapy before surgery)

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.

Group Type: EXPERIMENTAL

sunitinib malate

Intervention Type: DRUG

Given PO

paclitaxel

Intervention Type: DRUG

Given IV

doxorubicin hydrochloride

Intervention Type: DRUG

Given IV

cyclophosphamide

Intervention Type: DRUG

Given PO

filgrastim

Intervention Type: BIOLOGICAL

Given SC

therapeutic conventional surgery

Intervention Type: PROCEDURE

Undergo surgery

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

flow cytometry

Intervention Type: OTHER

Correlative studies

Interventions

sunitinib malate

Given PO

Intervention Type: DRUG

paclitaxel

Given IV

Intervention Type: DRUG

doxorubicin hydrochloride

Given IV

Intervention Type: DRUG

cyclophosphamide

Given PO

Intervention Type: DRUG

filgrastim

Given SC

Intervention Type: BIOLOGICAL

therapeutic conventional surgery

Undergo surgery

Intervention Type: PROCEDURE

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

flow cytometry

Correlative studies

Intervention Type: OTHER

Other Intervention Names

SU11248; sunitinib; Sutent; Anzatax; Asotax; TAX; Taxol; ADM; ADR; Adria; Adriamycin PFS; Adriamycin RDF; CPM; CTX; Cytoxan; Endoxan; Endoxana; G-CSF; Neupogen

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Jennifer Specht

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jennifer Specht

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

Anchorage Oncology Centre

Anchorage, Alaska, United States

Katmai Oncology Group

Anchorage, Alaska, United States

Arizona Cancer Center

Tucson, Arizona, United States

Saint Luke's Mountain States Tumor Institute

Boise, Idaho, United States

Skagit Valley Hospital

Mount Vernon, Washington, United States

Olympic Medical Center

Port Angeles, Washington, United States

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

Other Identifiers

NCI-2010-00607

Identifier Type: REGISTRY

Identifier Source: secondary_id

6488

Identifier Type: -

Identifier Source: org_study_id

NCT00831584

Identifier Type: -

Identifier Source: nct_alias