CClinicalTrials.gg
CompletedNCT00513695Updated Aug 7, 2019Results posted

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

A Phase 2 interventional study of sunitinib malate and paclitaxel in Inflammatory Breast Cancer, Male Breast Cancer and Stage II Breast Cancer, sponsored by University of Washington. Completed at 7 sites in United States. Per ClinicalTrials.gov, last updated 2019-08-07.

Sponsored by University of Washington · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
68
Allocation
Non-randomized
Sex
All
01

Study 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

Read the 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.

02

Conditions studied

  • Inflammatory Breast Cancer
  • Male Breast Cancer
  • Stage II Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
03

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 68 is close to the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

University of Washington is the lead sponsor of 1,397 studies on the registry; 225 are open to participants now.

Of its 154 completed or terminated interventional studies of FDA-regulated products, 132 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
68 participants (actual)

Study arms

  • 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 · Drug: paclitaxel · Drug: doxorubicin hydrochloride · Drug: cyclophosphamide · Biological: filgrastim · Procedure: therapeutic conventional surgery · Other: laboratory biomarker analysis · Other: flow cytometry

Interventions

  • Drugsunitinib malate

    Given PO

    Also known as: SU11248, sunitinib, Sutent

  • Drugpaclitaxel

    Given IV

    Also known as: Anzatax, Asotax, TAX, Taxol

  • Drugdoxorubicin hydrochloride

    Given IV

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

  • Drugcyclophosphamide

    Given PO

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

  • Biologicalfilgrastim

    Given SC

    Also known as: G-CSF, Neupogen

  • Proceduretherapeutic conventional surgery

    Undergo surgery

  • Otherlaboratory biomarker analysis

    Correlative studies

  • Otherflow cytometry

    Correlative studies

06

What researchers measure

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.

    Time frame: At the time of surgery

Secondary outcomes

  1. 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

  2. Relapse Rate

    Cumulative incidence rate of relapse, assessed at two years. Death is considered a competing risk.

    Time frame: Up to two years

  3. Time to Disease Progression

    Median time to disease progression, at two years, as defined by clear increase in disease sites present at registration or development of new disease sites.

    Time frame: Up to 2 years

  4. Overall Survival

    Kaplan-Meier estimate 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 at two years.

    Time frame: Up to 2 years

  5. Number and Percent of Subjects Reporting Adverse Events

    See Adverse Events section for more details.

    Time frame: 28 days after the last dose of study drug

07

Results

Posted May 10, 2017

Participant flow

Participant flow — Overall Study
MilestoneTreatment (Neoadjuvant Chemotherapy Before Surgery)
Started68
Completed63
Not completed5
Withdrew: Discontinued therapy2
Withdrew: Progression prior to surgery3

Outcome measures

PrimaryMicroscopic 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.

Time frame:
At the time of surgery
Reported as:
Number · percent of evaluable participants
Microscopic Pathologic CR (pCR) Rate
percent of evaluable participantsTreatment (Neoadjuvant Chemotherapy Before Surgery)
Microscopic Pathologic CR (pCR) Rate27 (18 to 39)
SecondaryClinical 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

No measurements were reported for this outcome.

SecondaryRelapse Rate

Cumulative incidence rate of relapse, assessed at two years. Death is considered a competing risk.

Time frame:
Up to two years
Reported as:
Number · probability of relapse
Relapse Rate
probability of relapseTreatment (Neoadjuvant Chemotherapy Before Surgery)
Relapse Rate0.215 (0.125 to 0.322)
SecondaryTime to Disease Progression

Median time to disease progression, at two years, as defined by clear increase in disease sites present at registration or development of new disease sites.

Time frame:
Up to 2 years
Reported as:
Median · days
Time to Disease Progression
daysTreatment (Neoadjuvant Chemotherapy Before Surgery)
Time to Disease ProgressionNA (NA to NA)
SecondaryOverall Survival

Kaplan-Meier estimate 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 at two years.

Time frame:
Up to 2 years
Reported as:
Number · survival probability
Overall Survival
survival probabilityTreatment (Neoadjuvant Chemotherapy Before Surgery)
Overall Survival0.875 (0.798 to 0.960)
SecondaryNumber and Percent of Subjects Reporting Adverse Events

See Adverse Events section for more details.

Time frame:
28 days after the last dose of study drug
Reported as:
Count of participants · Participants
Number and Percent of Subjects Reporting Adverse Events
ParticipantsTreatment (Neoadjuvant Chemotherapy Before Surgery)
Number and Percent of Subjects Reporting Adverse Events67

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (Neoadjuvant Chemotherapy Before Surgery)—47/68 (69.1%)67/68 (98.5%)
Most frequent serious events
Showing 10 of 12
Most frequent serious events
EventTreatment (Neoadjuvant Chemotherapy Before Surgery)
Neutropenia (ANC)Blood and lymphatic system disorders47/68
LeucopeniaBlood and lymphatic system disorders23/68
AnemiaBlood and lymphatic system disorders15/68
MucositisRespiratory, thoracic and mediastinal disorders7/68
ALT elevationInvestigations4/68
FatigueGeneral disorders3/68
DiarrheaGastrointestinal disorders3/68
Sensory NeuropathyNervous system disorders3/68
PainGeneral disorders2/68
Nail changesSkin and subcutaneous tissue disorders2/68
Most frequent other events
Showing 10 of 15
Most frequent other events
EventTreatment (Neoadjuvant Chemotherapy Before Surgery)
FatigueGeneral disorders37/68
LeucopeniaBlood and lymphatic system disorders34/68
AnemiaBlood and lymphatic system disorders32/68
Neutropenia (ANC)Blood and lymphatic system disorders22/68
PainGeneral disorders15/68
Nail changesSkin and subcutaneous tissue disorders12/68
DiarrheaGastrointestinal disorders9/68
RashSkin and subcutaneous tissue disorders8/68
HypertensionVascular disorders8/68
HeartburnGastrointestinal disorders8/68

Baseline characteristics

Age, Continuous
Age, Continuous(years)Treatment (Neoadjuvant Chemotherapy Before Surgery)
Median50 (33 to 79)
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (Neoadjuvant Chemotherapy Before Surgery)
Female68
Male0
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Treatment (Neoadjuvant Chemotherapy Before Surgery)
Hispanic or Latino4
Not Hispanic or Latino56
Unknown or Not Reported8
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment (Neoadjuvant Chemotherapy Before Surgery)
American Indian or Alaska Native0
Asian4
Native Hawaiian or Other Pacific Islander0
Black or African American2
White50
More than one race4
Unknown or Not Reported8
08

Study locations

7 sites
  • Anchorage Oncology Centre
    Anchorage, Alaska 99508, United States
  • Katmai Oncology Group
    Anchorage, Alaska 99508, United States
  • Arizona Cancer Center
    Tucson, Arizona 85724-5024, United States
  • Saint Luke's Mountain States Tumor Institute
    Boise, Idaho 83712, United States
  • Skagit Valley Hospital
    Mount Vernon, Washington 98273, United States
  • Olympic Medical Center
    Port Angeles, Washington 98362, United States
  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
    Seattle, Washington 98109, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 7, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00513695
Lead sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
Responsible party
Jennifer Specht (Principal Investigator, University of Washington) — Principal investigator
First posted
Aug 9, 2007
Start date
Jun 2007
Primary completion
Aug 2012
Completion
Oct 16, 2017
Results posted
May 10, 2017
Last update
Aug 7, 2019

Study contacts

Jennifer Specht
principal investigator · Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2019. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion