Neoadjuvant Sunitinib With Paclitaxel/Carboplatin in Patients With Triple-Negative Breast Cancer
Information source: SCRI Development Innovations, LLC
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Breast Cancer
Intervention: Paclitaxel (Drug); Carboplatin (Drug); Sunitinib (Drug)
Phase: Phase 1/Phase 2
Status: Completed
Sponsored by: SCRI Development Innovations, LLC Official(s) and/or principal investigator(s): Denise A Yardley, M.D., Study Chair, Affiliation: SCRI Development Innovations, LLC
Summary
This trial will examine the combination of sunitinib plus paclitaxel and carboplatin as
neoadjuvant treatment for locally advanced breast cancer.
Clinical Details
Official title: Phase I/II Trial of Neoadjuvant Sunitinib Administered With Weekly Paclitaxel/Carboplatin in Patients With Locally Advanced Triple-Negative Breast Cancer
Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Phase II: Number of Subjects With Triple-Negative Breast Cancer Exhibiting Pathologic Complete Response of Neoadjuvant Treatment With Sunitinib/Paclitaxel/Carboplatin
Secondary outcome: Number of Participants With Adverse Events as a Measure of Safety and TolerabilityOverall Response Rate (ORR) Disease-free Survival Overall Survival (OS)
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Female.
Criteria:
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
Locations and Contacts
Holy Cross Hospital, Ft. Lauderdale, Florida 33308, United States
Florida Cancer Specialists North, Ft. Myers, Florida 33916, United States
Florida Cancer Specialists South, Ft. Myers, Florida 33916, United States
Northeast Georgia Medical Center, Gainesville, Georgia 30501, United States
Providence Medical Group, Terre Haute, Indiana 47802, United States
Baptist Hospital East, Louisville, Kentucky 40207, United States
Center for Cancer and Blood Disorders, Bethesda, Maryland 20817, United States
National Capital Clinical Research Consortium, Bethesda, Maryland 20817, United States
St. Louis Cancer Care, Chesterfield, Missouri 63017, United States
Nebraska Methodist Cancer Center, Omaha, Nebraska 68114, United States
Hematology Oncology Associates of Northern NJ, Morristown, New Jersey 07960, United States
Cancer Centers of Southwest Oklahoma, Lawton, Oklahoma 73505, United States
Family Cancer Center, Collierville, Tennessee 38017, United States
Tennessee Oncology, PLLC, Nashville, Tennessee 37023, United States
Additional Information
Starting date: June 2009
Last updated: April 30, 2015
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