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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


Phase 2
N/A
N/A
Open (Enrolling)
Both
Inflammatory Breast Cancer, Male Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer

Thank you

Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Microscopic pathologic CR (pCR) rate

Outcome Description:

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.

Outcome Time Frame:

At the time of surgery

Safety Issue:

No

Principal Investigator

Jennifer Specht

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Institutional Review Board

Study ID:

6488

NCT ID:

NCT00513695

Start Date:

June 2007

Completion Date:

Related Keywords:

  • Inflammatory Breast Cancer
  • Male Breast Cancer
  • Stage II Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Breast Neoplasms
  • Breast Neoplasms, Male
  • Inflammatory Breast Neoplasms

Name

Location

Arizona Cancer CenterTucson, Arizona  85724
Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
Olympic Medical CenterPort Angeles, Washington  98362
Katmai Oncology GroupAnchorage, Alaska  99508-4627
Anchorage Oncology CentreAnchorage, Alaska  99508
Saint Luke's Mountain States Tumor InstituteBoise, Idaho  83712
Skagit Valley HospitalMt. Vernon, Washington  98273