Neoadjuvant Sunitinib With Paclitaxel/Carboplatin in Patients With Triple-Negative Breast Cancer

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
SCRI Development Innovations, LLC Identifier:
First received: April 22, 2009
Last updated: April 9, 2014
Last verified: April 2014

This open label, Phase I/II trial is designed to evaluate the combination of sunitinib plus paclitaxel and carboplatin as neoadjuvant treatment for locally advanced breast cancer. The Phase I portion of this study will determine the maximum tolerated dose (MTD) of paclitaxel, sunitinib and carboplatin that can be used together as neoadjuvant treatment in patients with locally advanced breast cancer. The MTD identified in the Phase I portion of the study will be used in the Phase II portion which will evaluate the efficacy, safety, and tolerability of neoadjuvant sunitinib/paclitaxel/carboplatin given for 6 cycles in patients with locally advanced breast cancer.

Condition Intervention Phase
Breast Cancer
Drug: Paclitaxel
Drug: Carboplatin
Drug: Sunitinib
Phase 1
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: Phase I/II Trial of Neoadjuvant Sunitinib Administered With Weekly Paclitaxel/Carboplatin in Patients With Locally Advanced Triple-Negative Breast Cancer

Resource links provided by NLM:

Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Phase I: To determine the maximum tolerated dose (MTD) of the combination of sunitinib/paclitaxel/carboplatin when used as neoadjuvant treatment for breast cancer. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Phase II: To evaluate the pathologic complete response rate of neoadjuvant treatment with sunitinib/paclitaxel/carboplatin in patients with triple-negative breast cancer. [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To characterize the safety and tolerability of neoadjuvant sunitinib/paclitaxel/carboplatin in patients with triple-negative breast cancer. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • To evaluate the efficacy of neoadjuvant sunitinib/paclitaxel/carboplatin in patients with triple-negative breast cancer. Secondary efficacy endpoints will include overall response rate, disease-free survival, and overall survival. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To evaluate the feasibility and safety of single agent maintenance sunitinib following neoadjuvant chemotherapy for triple-negative breast cancer. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 53
Study Start Date: June 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I-sunitinib/paclitaxel/carboplatin
Systemic Therapy
Drug: Paclitaxel
IV infusion per institutional guidelines on Days 1, 8 and 15 of a 28 day cycle as follows depending on dose level (DL): DL1- 70 mg/m2, DL2- 80 mg/m2, DL3- 80mg/m2, DL4- 80mg/m2, DL-1- 70mg/m2, DL-2- 60mg/m2
Other Names:
  • Paclitaxel
  • Taxol
  • Systemic Therapy
Drug: Carboplatin
IV infusion per institutional guidelines Day 1 of a 28 day cycle as follows depending on dose level (DL): DL1- AUC=5, DL2- AUC=5, DL3- AUC=6, DL4- AUC=6, DL-1- AUC=4, DL-2- AUC=4
Other Names:
  • Carboplatin
  • Paraplatin
  • Systemic Therapy
Drug: Sunitinib
By mouth (PO) once daily on days 1-21 of a 28 day cycle as follows depending on dose level (DL): DL1- 25mg, DL2-25mg, DL3- 25mg, DL4- 37.5mg, DL-1- 25mg, DL-2- 25mg
Other Names:
  • Sunitinib
  • Sutent
  • Systemic Therapy
Experimental: Phase II- sunitinib/paclitaxel/carboplatin
Systemic Therapy based on maximum tolerated dose (MTD) of the Phase I portion
Drug: Paclitaxel
IV infusion per institutional guidelines on Days 1, 8 and 15 of a 28 day cycle followed by Carboplatin and Sunitinib. Dosing determined by maximum tolerated dose (MTD) in Phase I portion
Other Names:
  • Paclitaxel
  • Taxol
  • Systemic Therapy
Drug: Carboplatin
IV infusion per institutional guidelines on Day 1 of a 28 day cycle following Paclitaxel
Other Names:
  • Carboplatin
  • Paraplatin
  • Systemic Therapy
Drug: Sunitinib
by mouth (PO) once daily on Days 1-21 of a 28 day cycle
Other Names:
  • Sunitinib
  • Sutent


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Female patients, age ≥18 years
  2. Histologically confirmed invasive ER-, PR-, and HER2-negative (triple-negative) adenocarcinoma of the breast
  3. Triple-negative tumors are defined as:

    • For HER2-negative:

      • Fluorescence in situ hybridization (FISH)-negative (defined by ratio <2.2) OR
      • Immunohistochemical (IHC) 0, IHC 1+, OR
      • IHC 2+ or IHC 3+ and FISH-negative (defined by ratio <2.2)
    • For ER- and PR-negative: <10% tumor staining by immunohistochemistry (IHC)
  4. Primary palpable disease confined to a breast and axilla on physical examination. For patients without clinically suspicious axillary adenopathy, the primary tumor must be larger than 2 cm in diameter by physical exam or imaging studies (clinical T2-T3, N0-N1, M0). For patients with clinically suspicious axillary adenopathy, the primary breast tumor can be any size (clinical T1-3, N1-2, M0). T1N0M0 lesions are excluded. Patients with metastatic disease are excluded
  5. Patients without clearly defined palpable breast mass or axillary lymph nodes but radiographically measurable tumor masses are eligible. Accepted procedures for measuring breast disease are mammography, MRI, and breast ultrasound. Patients with lesions measurable only by imaging will require repeat imaging after 3 cycles and prior to surgery
  6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2
  7. Neuropathy grade <1 by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v 3.0)
  8. Resolution of all acute effects of surgical procedures to grade ≤1. For patients who had, or will have sentinel lymph node and/or axillary dissection prior to initiation of study treatment, completion at least 4 weeks prior to starting study treatment and well-healed wound is required
  9. Adequate hematologic function with:

    • Absolute neutrophil count (ANC) >1500/μL
    • Platelets ≥100,000/μL
    • Hemoglobin ≥10 g/dL
  10. Adequate hepatic and renal function with:

    • Serum bilirubin ≤ the institutional upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x institutional ULN
    • Alkaline phosphatase ≤2.5 x institutional ULN
    • Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥40 mL/min
  11. Left ventricular ejection fraction (LVEF) ≥50% by multigated acquisition (MUGA) or echocardiogram (ECHO)
  12. Bilateral, synchronous breast cancer is allowed if one primary tumor meets the inclusion criteria
  13. Knowledge of the investigational nature of the study and ability to provide consent for study participation
  14. Ability and willingness to comply with study visits, treatment, testing, and other study procedures

Exclusion Criteria:

  1. Previous treatment for this breast cancer
  2. Previous treatment with paclitaxel or carboplatin
  3. Previous treatment with sunitinib or other angiogenic inhibitors (including, but not limited to bevacizumab, sorafenib, thalidomide)
  4. Any of the following within the 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolus
  5. Uncontrolled hypertension (blood pressure >150/100 mmHg despite optimal medical therapy)
  6. Ongoing cardiac dysrhythmias grade ≥2, atrial fibrillation of any grade, or prolongation of the QTc interval to >470 msec
  7. Major surgery, significant traumatic injury, or radiation therapy within 4 weeks of starting study treatment. An interval of at least 1 week is required following minor surgical procedures, with the exception of placement of a vascular access device
  8. Grade 3 hemorrhage within 4 weeks of starting study treatment
  9. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
  10. Known human immunodeficiency virus (HIV) infection or other serious infection
  11. Concomitant treatment with drugs having proarrhythmic potential including terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, and flecainide
  12. Concurrent use of the potent CYP3A4 inhibitors ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine and voriconazole and CYP3A4 inducers rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, St. John's Wort, and dexamethasone. Use of dexamethasone for study premedication is allowed. Grapefruit and grapefruit juice is prohibited. Alternative therapies should be used when available. If use of a potent CYP3A4 inhibitor or inducer is necessary, this must be approved by the Study Chair
  13. Known or suspected hypersensitivity to drugs containing Cremophor®EL (polyoxyethylated castor oil) such as cyclosporine or teniposide
  14. Pregnancy or breast-feeding. Negative serum pregnancy test is required within 7 days prior to first study treatment (Day 1, Cycle 1) for all women of childbearing potential. Patients of childbearing potential must agree to use a birth control method that is approved by their study physician while receiving study treatment and for three months after the last dose of study treatment. Patients must agree to not breast-feed while receiving study treatment
  15. Concurrent treatment with an ovarian hormonal replacement therapy or with hormonal agents such as raloxifene, tamoxifen or other selective estrogen receptor modulator (SERM). Patients must have discontinued use of such agents prior to beginning study treatment
  16. History of malignancy treated with curative intent within the previous 5 years with the exception of skin cancer, cervical carcinoma in situ, or follicular thyroid cancer. Patients with previous invasive cancers (including breast cancer) are eligible if the treatment was completed more than 5 years prior to initiating current study treatment, and there is no evidence of recurrent disease
  17. Use of any investigational agent within 30 days of administration of the first dose of study drug or concurrent treatment on another clinical study
  18. Requirement for radiation therapy concurrent with study anticancer treatment. Patients who require breast or chest wall radiation therapy after surgery are eligible, but will have maintenance sunitinib interrupted while receiving radiation
  19. Any other disease(s), psychiatric condition, metabolic dysfunction, or findings from a physical examination or clinical laboratory test result that would cause reasonable suspicion of a disease or condition, that contraindicates the use of study drugs, that may increase the risk associated with study participation, that may affect the interpretation of the results, or that would make the patient inappropriate for this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00887575

United States, Florida
Holy Cross Hospital
Ft. Lauderdale, Florida, United States, 33308
Florida Cancer Specialists South
Ft. Myers, Florida, United States, 33916
Florida Cancer Specialists North
Ft. Myers, Florida, United States, 33916
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Indiana
Providence Medical Group
Terre Haute, Indiana, United States, 47802
United States, Kentucky
Baptist Hospital East
Louisville, Kentucky, United States, 40207
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
National Capital Clinical Research Consortium
Bethesda, Maryland, United States, 20817
United States, Missouri
St. Louis Cancer Care
Chesterfield, Missouri, United States, 63017
United States, Nebraska
Nebraska Methodist Cancer Center
Omaha, Nebraska, United States, 68114
United States, New Jersey
Hematology Oncology Associates of Northern NJ
Morristown, New Jersey, United States, 07960
United States, Oklahoma
Cancer Centers of Southwest Oklahoma
Lawton, Oklahoma, United States, 73505
United States, Tennessee
Family Cancer Center
Collierville, Tennessee, United States, 38017
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37023
Sponsors and Collaborators
SCRI Development Innovations, LLC
Study Chair: Denise A Yardley, M.D. SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC Identifier: NCT00887575     History of Changes
Other Study ID Numbers: SCRI BRE 122
Study First Received: April 22, 2009
Last Updated: April 9, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by SCRI Development Innovations, LLC:
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors processed this record on September 11, 2014