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Trial record 1 of 1 for:    NCT00887575
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Neoadjuvant Sunitinib With Paclitaxel/Carboplatin in Patients With Triple-Negative Breast Cancer

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ClinicalTrials.gov Identifier: NCT00887575
Recruitment Status : Completed
First Posted : April 24, 2009
Results First Posted : December 17, 2014
Last Update Posted : September 7, 2016
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Tracking Information
First Submitted Date  ICMJE April 22, 2009
First Posted Date  ICMJE April 24, 2009
Results First Submitted Date  ICMJE November 21, 2014
Results First Posted Date  ICMJE December 17, 2014
Last Update Posted Date September 7, 2016
Study Start Date  ICMJE June 2009
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 2, 2016)
Phase II: The Number of Subjects Exhibiting Pathologic Complete Response to Neoadjuvant Treatment With Sunitinib/Paclitaxel/Carboplatin [ Time Frame: at weeks 26-30 ]
Pathologic complete response (PCR) is defined as no residual invasive breast cancer in final breast or axillary lymph node samples.
Original Primary Outcome Measures  ICMJE
 (submitted: April 23, 2009)
  • 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 ]
  • Phase II: To evaluate the pathologic complete response rate of neoadjuvant treatment with sunitinib/paclitaxel/carboplatin in patients with triplenegative breast cancer. [ Time Frame: 18 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2014)
  • Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Days 1, 8, and 15 of each 4-week cycle up to 24 weeks during neoadjuvant treatment, and every 4 weeks during maintenance treatment ]
    Assessments will be made through analysis of reported incidence of treatment-emergent adverse events (AEs) and serious adverse events (SAEs) at the phase II dose
  • Overall Response Rate (ORR) [ Time Frame: Days 1, 8 and 15 of each cycle, minimum of 12 weeks ]
    Assessed by clinical, radiologic and surgical determinations before and after neoadjuvant therapy. Measurable lesions will be defined by RECIST criteria v1.1.
  • Disease-free Survival [ Time Frame: every 4 weeks from date of surgery until treatment discontinuation or death, expected average 18 months ]
    Defined as the time between day of surgery to first documented disease occurrence or death due to any cause.
  • Overall Survival (OS) [ Time Frame: 24 months ]
    Defined as the time between Day 1 Cycle 1 to time of death from any cause.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2009)
  • To characterize the safety and tolerability of neoadjuvant sunitinib/paclitaxel/carboplatin in patients with triple-negative breast cancer. [ Time Frame: 18 months ]
  • 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 ]
  • To evaluate the feasibility and safety of single agent maintenance sunitinib following neoadjuvant chemotherapy for triple-negative breast cancer. [ Time Frame: 18 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neoadjuvant Sunitinib With Paclitaxel/Carboplatin in Patients With Triple-Negative Breast Cancer
Official Title  ICMJE Phase I/II Trial of Neoadjuvant Sunitinib Administered With Weekly Paclitaxel/Carboplatin in Patients With Locally Advanced Triple-Negative Breast Cancer
Brief Summary This trial will examine the combination of sunitinib plus paclitaxel and carboplatin as neoadjuvant treatment for locally advanced breast cancer.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • 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:
    • 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:
    • 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. Maintenance therapy of 25mg daily
    Other Names:
    • Sutent
    • Systemic Therapy
Study Arms  ICMJE
  • Experimental: Dose Level I

    Neoadjuvant - Paclitaxel IV (70 mg/m^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 5) day 1 of every cycle and Sunitinib PO (25mg) daily.

    Maintenance - Sunitinib PO (25mg) daily

    Interventions:
    • Drug: Paclitaxel
    • Drug: Carboplatin
    • Drug: Sunitinib
  • Experimental: Dose Level II
    Paclitaxel IV (80 mg/m^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 5) day 1 of every cycle and Sunitinib PO (25mg) daily.
    Interventions:
    • Drug: Paclitaxel
    • Drug: Carboplatin
    • Drug: Sunitinib
  • Experimental: Dose Level III
    Paclitaxel IV (80 mg/m^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 6) day 1 of every cycle and Sunitinib PO (25mg) daily.
    Interventions:
    • Drug: Paclitaxel
    • Drug: Carboplatin
    • Drug: Sunitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 9, 2014)
54
Original Estimated Enrollment  ICMJE
 (submitted: April 23, 2009)
53
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 1week 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, rifapentine, 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 ) 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00887575
Other Study ID Numbers  ICMJE SCRI BRE 122
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party SCRI Development Innovations, LLC
Study Sponsor  ICMJE SCRI Development Innovations, LLC
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Study Chair: Denise A Yardley, M.D. SCRI Development Innovations, LLC
PRS Account SCRI Development Innovations, LLC
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP