A Randomized Trial of Ixempra Versus Taxol in Adjuvant Therapy of Triple Negative Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT00789581
- Lead Sponsor
- SCRI Development Innovations, LLC
- Brief Summary
This is a randomized, Phase III, open-label, multicenter study.
- Detailed Description
Patients will be randomized in a 1:1 ratio to receive one of two different treatment arms. Patients in treatment arm 1 will receive AC followed by ixabepilone. Patients in treatment arm 2 will receive AC followed by weekly paclitaxel.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 614
-
Female patients greater than or equal to18 years of age.
-
Histologically confirmed invasive unilateral breast cancer (regardless of
histology).
-
Early-stage breast cancer, defined as:
- Node-positive disease: >0.2-mm metastasis in at least one lymph node (pN1mipN2b)OR
- Node-negative, with primary tumor >1.0 cm (T1c-T3).
-
Definitive loco-regional surgery must have been completed as specified
below:
-
Patients must have undergone either breast conservation surgery
(i.e., lumpectomy) or total mastectomy.
-
Surgical margins of the resected section must be histologically free of
invasive adenocarcinoma and ductal carcinoma in situ.
- Surgical margins involved with lobular carcinoma in situ (LCIS) will not
be considered as a positive margin; therefore, such patients will be eligible for this study without additional resection.
- Patients must have completed axillary lymph node sampling for the pathologic evaluation of axillary lymph nodes as specified below:
Sentinel node biopsy and/or either lymph node sampling procedure or axillary dissection.
-
-
Multicentric and multifocal invasive breast cancer is eligible if loco-regional surgery has been completed as described above.
-
Patients with synchronous bilateral cancers are eligible only if:
- All cancers are of triple-negative phenotype, defined as ER-, PR-, HER2-.
- Eligibility based on the highest stage grouping.
-
HER2 negative tumors. HER2 negativity must be confirmed by one of the
following:
- FISH-negative (FISH ratio <2.2), or
- IHC 0-1+, or
- IHC 2-3+ AND FISH-negative (FISH ratio <2.2).
-
Estrogen receptor negative (<10% staining by IHC for estrogen receptor).
-
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
-
Patient must be <= 84 days from having completed definitive primary breast surgery (either lumpectomy or mastectomy).
-
MammoSite brachytherapy radiation is acceptable if it is performed
immediately following surgery and prior to chemotherapy. It is recommended that chemotherapy be started no earlier than 2 weeks following the removal of the MammoSite balloon catheter.
-
Adequate hematologic function, defined by:
- Absolute neutrophil count (ANC) >1500/mm3
- Platelet count >=100,000/mm3
- Hemoglobin >9 g/dL
-
Adequate liver function, defined by:
- AST and ALT <=2.5 x the upper limit of normal (ULN)
- Total bilirubin <=1.5 x ULN (unless the patient has grade 1 bilirubin
elevation due to Gilbert's disease or a similar syndrome involving slow
conjugation of bilirubin).
-
Adequate renal function, defined by:
- Serum creatinine <=1.5 x ULN
-
Complete staging work-up <=12 weeks prior to initiation of study treatment
with computed tomography (CT) scans of the chest and abdomen/pelvis (abdomen/pelvis preferred; abdomen accepted), and either a positron emission tomography (PET) scan or a bone scan.
-
Adequate cardiac function, defined by a left ventricular ejection fraction
(LVEF) value of >50% (or normal per institutional guidelines) by MUGA scan or echocardiogram (ECHO).
-
Adequate recovery from recent surgery. At least 1 week must have elapsed from the time of a minor surgery (i.e., sentinel node biopsy, port-acath (placement); at least 3 weeks must have elapsed from the time of a major surgery (i.e., lumpectomy, partial or total mastectomy, axillary lymph node dissection, breast reconstruction procedure).
-
Patients with previous history of invasive cancers (including breast cancer)
are eligible if definitive treatment was completed more than 5 years prior to
initiating current study treatment, and there is no evidence of recurrent disease.
-
Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
-
Patient must be accessible for treatment and follow-up.
-
Women of childbearing potential must agree to use an acceptable method of birth control to avoid pregnancy for the duration of study treatment, and for 3 months thereafter.
-
All patients must be able to understand the investigational nature of the
study and give written informed consent prior to study entry.
-
Women who are pregnant or breastfeeding.
-
History of previous diagnosis of invasive breast cancer (unless treated >5 years previously with no recurrence). History of previously treated ductal carcinoma in situ (DCIS) is acceptable.
-
Any evidence or suspicion of metastatic disease other than ipsilateral
axillary lymph nodes.
-
Any tumor >=T4 (cutaneous invasion, deep adherence, inflammatory breast cancer).
-
Previous anthracycline chemotherapy.
-
Concurrent use of CYP3A4 inhibitors from 72 hours prior to initiation of
study treatment until the end of treatment with ixabepilone.
-
Previous treatment for this breast cancer (including neoadjuvant
chemotherapy).
-
Previous cancer (with the exception of non-melanoma skin cancer or cervical carcinoma in situ) in the past 5 years (including invasive contralateral breast cancer).
-
Peripheral neuropathy of > grade 1 per NCI CTCAE v3.0.
-
Cardiac disease, including: congestive heart failure (CHF) > Class II per
New York Heart Association (NYHA) classification; unstable angina (anginal symptoms at rest) or new-onset angina (i.e., began within the last 3 months), or myocardial infarction within the past 6 months; symptomatic CHF, unstable angina pectoris, cardiac arrhythmia, or cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
-
History of hypersensitivity to CremophorEL (polyoxyethylated castor oil) or
a drug formulated in CremophorEL such as paclitaxel.
-
Use of any investigational agent within 30 days of administration of the first dose of study drug.
-
Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
-
Concurrent severe, uncontrolled infection or intercurrent illness including,
but not limited to, ongoing or active infection, or psychiatric illness/social
situations that would limit compliance with study requirements.
-
Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
-
Inability to comply with study and/or follow-up procedures.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Doxorubicin/cyclophosphamide, ixabepilone Cyclophosphamide Doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 administered for 4 cycles of 21 days each, followed by ixabepilone at 40 mg/m2 given for 4 cycles of 21 days each. Doxorubicin/cyclophosphamide, paclitaxel Cyclophosphamide Doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 administered for 4 cycles of 21 days each, followed by paclitaxel at 80 mg/m2 weekly for 12 weeks. Doxorubicin/cyclophosphamide, ixabepilone Ixabepilone (Ixempra) Doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 administered for 4 cycles of 21 days each, followed by ixabepilone at 40 mg/m2 given for 4 cycles of 21 days each. Doxorubicin/cyclophosphamide, paclitaxel Doxorubicin Doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 administered for 4 cycles of 21 days each, followed by paclitaxel at 80 mg/m2 weekly for 12 weeks. Doxorubicin/cyclophosphamide, paclitaxel Paclitaxel (Taxol) Doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 administered for 4 cycles of 21 days each, followed by paclitaxel at 80 mg/m2 weekly for 12 weeks. Doxorubicin/cyclophosphamide, ixabepilone Doxorubicin Doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 administered for 4 cycles of 21 days each, followed by ixabepilone at 40 mg/m2 given for 4 cycles of 21 days each.
- Primary Outcome Measures
Name Time Method Disease-free Survival up to 5.25 years (63 months) The percentage of participants with disease-free survival at 3 and 5 years. Disease-free survival (DFS) is measured from the time between randomization and the date of first documented disease recurrence, or death from any cause.
- Secondary Outcome Measures
Name Time Method Overall Survival up to 5.25 years (63 months) The percentage of participants with overall survival at 3 and 5 years are presented. Overall survival (OS) defined as the time between randomization to date of death from any cause.
Trial Locations
- Locations (69)
Northeast Alabama Regional Medical Center
🇺🇸Anniston, Alabama, United States
Cancer Center of Huntsville
🇺🇸Huntsville, Alabama, United States
Clearview Cancer Institute
🇺🇸Huntsville, Alabama, United States
University of Southern Alabama
🇺🇸Mobile, Alabama, United States
Northeast Arkansas Clinic
🇺🇸Jonesboro, Arkansas, United States
Wilshire Oncology Medical Group
🇺🇸La Verne, California, United States
New Hope Cancer and Research Institute
🇺🇸Pomona, California, United States
Eastern Connecticut Hematology Oncology
🇺🇸Norwich, Connecticut, United States
Aventura Medical Center
🇺🇸Aventura, Florida, United States
Lynn Cancer Institute
🇺🇸Boca Raton, Florida, United States
Scroll for more (59 remaining)Northeast Alabama Regional Medical Center🇺🇸Anniston, Alabama, United States