- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00887575
Neoadjuvant Sunitinib With Paclitaxel/Carboplatin in Patients With Triple-Negative Breast Cancer
Phase I/II Trial of Neoadjuvant Sunitinib Administered With Weekly Paclitaxel/Carboplatin in Patients With Locally Advanced Triple-Negative Breast Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Florida
-
Ft. Lauderdale, Florida, United States, 33308
- Holy Cross Hospital
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Ft. Myers, Florida, United States, 33916
- Florida Cancer Specialists NORTH
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Ft. Myers, Florida, United States, 33916
- Florida Cancer Specialists South
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Georgia
-
Gainesville, Georgia, United States, 30501
- Northeast Georgia Medical Center
-
-
Indiana
-
Terre Haute, Indiana, United States, 47802
- Providence Medical Group
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Kentucky
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Louisville, Kentucky, United States, 40207
- Baptist Hospital East
-
-
Maryland
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Bethesda, Maryland, United States, 20817
- Center For Cancer And Blood Disorders
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Bethesda, Maryland, United States, 20817
- National Capital Clinical Research Consortium
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Missouri
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Chesterfield, Missouri, United States, 63017
- St. Louis Cancer Care
-
-
Nebraska
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Omaha, Nebraska, United States, 68114
- Nebraska Methodist Cancer Center
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New Jersey
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Morristown, New Jersey, United States, 07960
- Hematology Oncology Associates of Northern NJ
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-
Oklahoma
-
Lawton, Oklahoma, United States, 73505
- Cancer Centers of Southwest Oklahoma
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Tennessee
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Collierville, Tennessee, United States, 38017
- Family Cancer Center
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Nashville, Tennessee, United States, 37023
- Tennessee Oncology, PLLC
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 neutrophil 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 1week 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, 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
- 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 ) 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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 |
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:
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:
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:
|
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.
|
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:
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:
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:
|
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.
|
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:
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:
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:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
at weeks 26-30
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Days 1, 8, and 15 of each 4-week cycle up to 24 weeks during neoadjuvant treatment, and every 4 weeks during maintenance treatment
|
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.
|
Days 1, 8 and 15 of each cycle, minimum of 12 weeks
|
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.
|
every 4 weeks from date of surgery until treatment discontinuation or death, expected average 18 months
|
Overall Survival (OS)
Time Frame: 24 months
|
Defined as the time between Day 1 Cycle 1 to time of death from any cause.
|
24 months
|
Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Triple Negative Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Protein Kinase Inhibitors
- Carboplatin
- Paclitaxel
- Sunitinib
Other Study ID Numbers
- SCRI BRE 122
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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