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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT00513695
First received: August 8, 2007
Last updated: May 7, 2013
Last verified: May 2013
History of Changes
  Purpose

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


Condition Intervention Phase
Inflammatory Breast Cancer
Male Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
 Drug: sunitinib malate
Drug: paclitaxel
Drug: doxorubicin hydrochloride
Drug: cyclophosphamide
Biological: filgrastim
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Other: flow cytometry
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Evaluating the Safety and Efficacy of Sunitinib Maleate in Combination With Weekly Paclitaxel Followed by Doxorubicin and Daily Oral Cyclophosphamide Plus G-CSF as Neoadjuvant Chemotherapy for Locally Advanced or Inflammatory Breast Cancer

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Microscopic pathologic CR (pCR) rate [ Time Frame: At the time of surgery ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Clinical complete response and correlation with plasma VEGF, soluble VCAM (sVCAM), and circulating endothelial cells (CECs) levels [ Time Frame: At baseline, after week 12 of therapy, and prior to surgery ] [ Designated as safety issue: No ]
  • Relapse rate [ Time Frame: Every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter ] [ Designated as safety issue: No ]
  • Time to disease progression as defined by clear increase in disease sites present at registration or development of new disease sites [ Time Frame: From day 1 to the time the patient is first recorded as having disease progression, study termination, or date of death, assessed up to 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From the start of protocol therapy until the date of death from any cause or the last date the patient was known to be alive, assessed up to 2 years ] [ Designated as safety issue: No ]
  • Number and percent of subjects reporting adverse events (all, severe or worse, serious and related) [ Time Frame: 28 days after the last dose of study drug ] [ Designated as safety issue: Yes ]

Enrollment: 67
Study Start Date: June 2007
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
 Drug: sunitinib malate
Given PO
Other Names:
  • SU11248
  • sunitinib
  • Sutent
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cyclophosphamide
Given PO
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Procedure: therapeutic conventional surgery
Undergo surgery
Other: laboratory biomarker analysis
Correlative studies
Other: flow cytometry
Correlative studies

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00513695

Locations
United States, Alaska
Katmai Oncology Group
Anchorage, Alaska, United States, 99508
Anchorage Oncology Centre
Anchorage, Alaska, United States, 99508
United States, Arizona
Arizona Cancer Center
Tucson, Arizona, United States, 85724-5024
United States, Idaho
Saint Luke's Mountain States Tumor Institute
Boise, Idaho, United States, 83712
United States, Washington
Skagit Valley Hospital
Mt. Vernon, Washington, United States, 98273
Olympic Medical Center
Port Angeles, Washington, United States, 98362
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Investigators
Principal Investigator: Jennifer Specht Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT00513695     History of Changes
Obsolete Identifiers: NCT00831584
Other Study ID Numbers: 6488, NCI-2010-00607
Study First Received: August 8, 2007
Last Updated: May 7, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Inflammatory Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Sunitinib
Doxorubicin
Paclitaxel
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
 Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic
Adjuvants, Immunologic
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on May 23, 2013