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

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

This study is currently recruiting participants.
Study NCT00887575 Information provided by Sarah Cannon Research Institute
First Received: April 22, 2009 Last Updated: December 8, 2009 History of Changes

Tracking Information
First Received Date ICMJE April 22, 2009
Last Updated Date December 8, 2009
Start Date ICMJE June 2009
Estimated Primary Completion Date June 2010 (final data collection date for primary outcome measure)
Current 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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Original Primary Outcome Measures ICMJE Same as current
Change History Complete list of historical versions of study NCT00887575 on ClinicalTrials.gov Archive Site
Current 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 ] [ 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 ]

Original Secondary Outcome Measures ICMJE Same as current

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 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 in patients with locally advanced breast cancer.

Detailed Description
Study Phase Phase I, Phase II
Study Type ICMJE Interventional
Study Design ICMJE Treatment, Non-Randomized, Open Label, Single Group Assignment, Efficacy Study
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:
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
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 instutional 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

Study Arms / Comparison Groups Phase I: Experimental
Systemic Therapy
Interventions:
Drug: Paclitaxel
Drug: Carboplatin
Drug: Sunitinib
Phase II: Experimental
Systemic Therapy based on maximum tolerated dose (MTD) of the Phase I portion
Interventions:
Drug: Paclitaxel
Drug: Carboplatin
Drug: Sunitinib

Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status ICMJE Recruiting
Estimated Enrollment ICMJE 53
Estimated Completion Date June 2011
Estimated Primary Completion Date June 2010 (final data collection date for primary outcome measure)
Eligibility Criteria ICMJE Inclusion Criteria:

Female patients, age ≥18 years.
Histologically confirmed invasive ER-, PR-, and HER2-negative (triple-negative) adenocarcinoma of the breast.
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).
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.
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.
Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2.
Neuropathy grade <1 by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v 3.0).
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.
Adequate hematologic function with:

Absolute neutophil count (ANC) >1500/μL.
Platelets ≥100,000/μL.
Hemoglobin ≥10 g/dL.
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.
Left ventricular ejection fraction (LVEF) ≥50% by multigated acquisition (MUGA) or echocardiogram (ECHO).
Bilateral, synchronous breast cancer is allowed if one primary tumor meets the inclusion criteria.
Knowledge of the investigational nature of the study and ability to provide consent for study participation.
Ability and willingness to comply with study visits, treatment, testing, and other study procedures. -
Exclusion Criteria:

Previous treatment for this breast cancer.
Previous treatment with paclitaxel or carboplatin.
Previous treatment with sunitinib or other angiogenic inhibitors (including, but not limited to bevacizumab, sorafenib, thalidomide).
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.
Uncontrolled hypertension (blood pressure >150/100 mmHg despite optimal medical therapy).
Ongoing cardiac dysrhythmias grade ≥2, atrial fibrillation of any grade, or prolongation of the QTc interval to >470 msec.
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.
Grade 3 hemorrhage within 4 weeks of starting study treatment.
Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication.
Known human immunodeficiency virus (HIV) infection or other serious infection.
Concomitant treatment with drugs having proarrhythmic potential including terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, and flecainide.
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.
Known or suspected hypersensitivity to drugs containing Cremophor®EL (polyoxyethylated castor oil) such as cyclosporine or teniposide.
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.
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.
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.
Use of any investigational agent within 30 days of administration of the first dose of study drug or concurrent treatment on another clinical study.
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.
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. -

Gender Female
Ages 18 Years and older
Accepts Healthy Volunteers No
Contacts ICMJE Contact: Denise A Yardley, M.D. 615-329-7274 dyardley@tnonc.com
Contact: Trials Info 615-329-7274 trialsinfo@scresearch.net

Location Countries ICMJE United States

Administrative Information
NCT ID ICMJE NCT00887575
Responsible Party Denise A. Yardley, M.D., SCRI Oncology Research Consortium
Study ID Numbers ICMJE SCRI BRE 122
Study Sponsor ICMJE Sarah Cannon Research Institute
Collaborators ICMJE Pfizer
Investigators ICMJE Study Chair: Denise A Yardley, M.D. Sarah Cannon Research Institute

Information Provided By Sarah Cannon Research Institute
Verification Date December 2009