A Randomized Trial of Ixempra Versus Taxol in Adjuvant Therapy of Triple Negative Breast Cancer

Overview[ - collapse ][ - ]

Purpose This is a randomized, Phase III, open-label, multicenter study.
ConditionBreast Cancer
InterventionDrug: Doxorubicin
Drug: Cyclophosphamide
Drug: Ixabepilone (Ixempra)
Drug: Paclitaxel (Taxol)
PhasePhase 3
SponsorSCRI Development Innovations, LLC
Responsible PartySCRI Development Innovations, LLC
ClinicalTrials.gov IdentifierNCT00789581
First ReceivedNovember 11, 2008
Last UpdatedJanuary 22, 2014
Last verifiedJanuary 2014

Tracking Information[ + expand ][ + ]

First Received DateNovember 11, 2008
Last Updated DateJanuary 22, 2014
Start DateJanuary 2009
Estimated Primary Completion DateJanuary 2016
Current Primary Outcome MeasuresTo compare the disease-free survival (DFS) of women with triple-negative early-stage breast cancer following adjuvant treatment with AC followed by every-3-week ixabepilone vs. AC followed by weekly paclitaxel. [Time Frame: 5 years] [Designated as safety issue: No]
Current Secondary Outcome MeasuresTo compare the overall survival. To assess the safety. To compare the DFS. [Time Frame: 5 years] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitleA Randomized Trial of Ixempra Versus Taxol in Adjuvant Therapy of Triple Negative Breast Cancer
Official TitlePhase III Study of Doxorubicin/Cyclophosphamide (AC) Followed by Ixabepilone vs. AC Followed by Paclitaxel in Patients With Triple-Negative Early-Stage Breast Cancer
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.
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionBreast Cancer
InterventionDrug: Doxorubicin
Doxorubicin 60 mg/m2
Other Names:
  • Adriamycin
  • hydroxydaunorubicin
  • Adriamycin PFS
  • Adriamycin RDF
  • Rubex
Drug: Cyclophosphamide
Cyclophosphamide 600 mg/m2
Other Names:
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
  • Cytophosphane
Drug: Ixabepilone (Ixempra)
Ixabepilone 40 mg/m2
Other Names:
  • Ixempra
  • azaepothilone B
  • BMS-247550
Drug: Paclitaxel (Taxol)
Paclitaxel 80 mg/m2
Other Names:
Taxol
Study Arm (s)
  • Active Comparator: Doxorubicin/cyclophosphamide, ixabepilone
    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.
  • Active Comparator: Doxorubicin/cyclophosphamide, paclitaxel
    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.

Recruitment Information[ + expand ][ + ]

Recruitment StatusActive, not recruiting
Estimated Enrollment614
Estimated Completion DateJanuary 2016
Estimated Primary Completion DateJanuary 2015
Eligibility Criteria
Inclusion Criteria:

1. Female patients greater than or equal to18 years of age.

2. Histologically confirmed invasive unilateral breast cancer (regardless of histology).

3. 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).

4. 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.

5. Multicentric and multifocal invasive breast cancer is eligible if loco-regional
surgery has been completed as described above.

6. 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.

7. 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).

8. Estrogen receptor negative (<10% staining by IHC for estrogen receptor).

9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

10. Patient must be <= 84 days from having completed definitive primary breast surgery
(either lumpectomy or mastectomy).

11. 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.

12. Adequate hematologic function, defined by:

- Absolute neutrophil count (ANC) >1500/mm3

- Platelet count >=100,000/mm3

- Hemoglobin >9 g/dL

13. 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).

14. Adequate renal function, defined by:

· Serum creatinine <=1.5 x ULN

15. 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.

16. 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).

17. 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).

18. 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.

19. 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.

20. Patient must be accessible for treatment and follow-up.

21. 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.

22. All patients must be able to understand the investigational nature of the study and
give written informed consent prior to study entry.

Exclusion Criteria:

1. Women who are pregnant or breastfeeding.

2. 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.

3. Any evidence or suspicion of metastatic disease other than ipsilateral axillary lymph
nodes.

4. Any tumor >=T4 (cutaneous invasion, deep adherence, inflammatory breast cancer).

5. Previous anthracycline chemotherapy.

6. Concurrent use of CYP3A4 inhibitors from 72 hours prior to initiation of study
treatment until the end of treatment with ixabepilone.

7. Previous treatment for this breast cancer (including neoadjuvant chemotherapy).

8. 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).

9. Peripheral neuropathy of > grade 1 per NCI CTCAE v3.0.

10. 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.

11. History of hypersensitivity to CremophorEL (polyoxyethylated castor oil) or a drug
formulated in CremophorEL such as paclitaxel.

12. Use of any investigational agent within 30 days of administration of the first dose
of study drug.

13. Patients may not receive any other investigational or anti-cancer treatments while
participating in this study.

14. 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.

15. Mental condition that would prevent patient comprehension of the nature of, and risk
associated with, the study.

16. Inability to comply with study and/or follow-up procedures.
GenderFemale
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States, Puerto Rico

Administrative Information[ + expand ][ + ]

NCT Number NCT00789581
Other Study ID NumbersSCRI BRE 145
Has Data Monitoring CommitteeYes
Information Provided BySCRI Development Innovations, LLC
Study SponsorSCRI Development Innovations, LLC
CollaboratorsBristol-Myers Squibb
Investigators Study Chair: Denise A Yardley, M.D. SCRI Development Innovations, LLC
Verification DateJanuary 2014

Locations[ + expand ][ + ]

Northeast Alabama Regional Medical Center
Anniston, Alabama, United States, 36207
Cancer Center of Huntsville
Huntsville, Alabama, United States, 35801
Clearview Cancer Institute
Huntsville, Alabama, United States, 35805
University of Southern Alabama
Mobile, Alabama, United States, 36604
Northeast Arkansas Clinic
Jonesboro, Arkansas, United States, 72401
Wilshire Oncology Medical Group
LaVerne, California, United States, 91750
New Hope Cancer and Research Institute
Pomona, California, United States, 91767
Eastern Connecticut Hematology Oncology
Norwich, Connecticut, United States, 06360
Aventura Medical Center
Aventura, Florida, United States, 33180
Lynn Cancer Institute
Boca Raton, Florida, United States, 33428
Florida Cancer Care
Davie, Florida, United States, 33328
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
Holy Cross Hospital
Ft. Lauderdale, Florida, United States, 33308
Memorial Regional Cancer Center
Hollywood, Florida, United States, 33021
Integrated Community Oncology Network
Jacksonville, Florida, United States, 32256
Watson Clinic Center for Cancer Care and Research
Lakeland, Florida, United States, 33805
Space Coast Medical Associates
Titusville, Florida, United States, 32796
Piedmont Healthcare
Atlanta, Georgia, United States, 30309
Emory/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
Augusta Oncology Associates
Augusta, Georgia, United States, 30901
Medical Oncology Associates of Augusta
Augusta, Georgia, United States, 30901
Medical College of Georgia Cancer Specialists
Augusta, Georgia, United States, 30912
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
Suburban Hem Onc
Lawrenceville, Georgia, United States, 30045
Mid-Illinois Hematology & Oncology
Normal, Illinois, United States, 61761
Hematology Oncology of the North Shore
Skokie, Illinois, United States, 60076
Oncology Hematology Associates of SW Indiana
Evansville, Indiana, United States, 47714
Hematology Oncology of Indiana
Indianapolis, Indiana, United States, 46260
Providence Medical Group
Terre Haute, Indiana, United States, 47802
Kansas City Cancer Centers
Overland Park, Kansas, United States, 66210
Cotton O'Neil Cancer Center
Topeka, Kansas, United States, 66606
Consultants in Blood Disorders and Cancer
Louisville, Kentucky, United States, 40207
Baton Rouge General Medical Center
Baton Rouge, Louisiana, United States, 70806
Mercy Hospital
Portland, Maine, United States, 04101
Weinberg Cancer Institute at Franklin Square
Baltimore, Maryland, United States, 21237
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
Fallon Clinic
Worchester, Massachusetts, United States, 01608
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, United States, 49503
Fairview Medical Oncology Clinic
Edina, Minnesota, United States, 55436
St. Louis Cancer Care
Chesterfield, Missouri, United States, 63017
Research Medical Center
Kansas City, Missouri, United States, 64132
St. John's Clinic
Springfield, Missouri, United States, 65804
Methodist Cancer Center
Omaha, Nebraska, United States, 68114
St. Clare's Hospital Oncology and Hematology
Denville, New Jersey, United States, 07834
Hematology Oncology Associates of Northern NJ
Morristown, New Jersey, United States, 07960
Southern Oncology and Hematology
Vineland, New Jersey, United States, 08360
New Mexico Oncology Hematology Consultants
Albuquerque, New Mexico, United States, 87109
Alamance Regional Medical Center
Burlington, North Carolina, United States, 27215
Oncology Hematology Care
Cincinnati, Ohio, United States, 45242
Mid Ohio Oncology/Hematology, Inc./ The Mark H. Zangmeister Center
Columbus, Ohio, United States, 43219
Hematology/Oncology Inc
Elyria, Ohio, United States, 44035
Hickman Cancer Center (Flower Hospital)
Sylvania, Ohio, United States, 43560
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
Bux-Mont Oncology, Fox Chase Cancer Center
Rockledge, Pennsylvania, United States, 18960
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
South Carolina Oncology Associates, PA
Columbia, South Carolina, United States, 29210
Lowcountry Hematology Oncology
Mt. Pleasant, South Carolina, United States, 29464
Coastal Cancer Center
Myrtle Beach, South Carolina, United States, 29572
Spartanburg Regional Medical Center
Spartanburg, South Carolina, United States, 29303
Chattanooga Oncology Hematology Associates
Chattanooga, Tennessee, United States, 37404
Associates in Hematology Oncology
Chattanooga, Tennessee, United States, 37404
Family Cancer Center
Collierville, Tennessee, United States, 38017
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37023
Coastal Bend Cancer Center
Corpus Christi, Texas, United States, 78463
Center for Cancer and Blood Disorders
Ft. Worth, Texas, United States, 76104
Medical Oncology Methodist Hospital
Houston, Texas, United States, 77030
South Texas Oncology and Hematology
San Antonio, Texas, United States, 78258
Peninsula Cancer Institute
Newport News, Virginia, United States, 23601
Virginia Cancer Institute
Richmond, Virginia, United States, 23235
San Juan Hospital
San Juan, Puerto Rico