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Phase III Study of Doxorubicin/Cyclophosphamide (AC) Followed by Ixabepilone vs. AC Followed by Paclitaxel in Patients With Triple-Negative Early-Stage Breast Cancer


Phase 3
18 Years
N/A
Open (Enrolling)
Female
Breast Cancer

Thank you

Trial Information

Phase III Study of Doxorubicin/Cyclophosphamide (AC) Followed by Ixabepilone vs. AC Followed by Paclitaxel in Patients With Triple-Negative Early-Stage Breast Cancer


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.


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:

ยท 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.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To 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.

Outcome Time Frame:

5 years

Safety Issue:

No

Principal Investigator

Denise A Yardley, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Sarah Cannon Research Institute

Authority:

United States: Food and Drug Administration

Study ID:

SCRI BRE 145

NCT ID:

NCT00789581

Start Date:

January 2009

Completion Date:

January 2016

Related Keywords:

  • Breast Cancer
  • Breast Cancer
  • Adjuvant
  • Doxorubicin
  • Cyclophosphamide
  • Paclitaxel
  • Ixabepilone
  • TITAN
  • Breast Neoplasms

Name

Location

Medical University of South Carolina Charleston, South Carolina  29425-0721
Northeast Alabama Regional Medical Center Anniston, Alabama  36207
Northeast Arkansas Clinic Jonesboro, Arkansas  72401-3125
South Texas Oncology and Hematology San Antonio, Texas  78229
Memorial Regional Cancer Center Hollywood, Florida  33021
Florida Cancer Specialists Fort Myers, Florida  33901
University of Pittsburgh Medical Center Pittsburgh, Pennsylvania  15213
Northeast Georgia Medical Center Gainesville, Georgia  30501
Spartanburg Regional Medical Center Spartanburg, South Carolina  29303
Research Medical Center Kansas City, Missouri  64132
Consultants in Blood Disorders and Cancer Louisville, Kentucky  40207
Baton Rouge General Medical Center Baton Rouge, Louisiana  70821-2511
Integrated Community Oncology Network Jacksonville Beach, Florida  32250
South Carolina Oncology Associates, PA Columbia, South Carolina  29210
Family Cancer Center Collierville, Tennessee  38017
Holy Cross Hospital Fort Lauderdale, Florida  33308
Coastal Cancer Center Myrtle Beach, South Carolina  29572
New Mexico Oncology Hematology Consultants Albuquerque, New Mexico  87102
Augusta Oncology Associates Augusta, Georgia  30901
Virginia Cancer Institute Richmond, Virginia  23230
Wilshire Oncology Medical Group Glendora, California  91741
Methodist Cancer Center Omaha, Nebraska  68114
Medical Oncology Associates of Augusta Augusta, Georgia  30901
Peninsula Cancer Institute Newport News, Virginia  23601
Center for Cancer and Blood Disorders Bethesda, Maryland  20817
Clearview Cancer Institute Huntsville, Alabama  35805
Mercy Hospital Portland, Maine  04101
Grand Rapids Clinical Oncology Program Grand Rapids, Michigan  49503
Alamance Regional Medical Center Burlington, North Carolina  27216
Space Coast Medical Associates Cocoa Beach, Florida  32931
Kansas City Cancer Centers Lenexa, Kansas  
St. Louis Cancer Care Chesterfield, Missouri  63017
Tennessee Oncology, PLLC Clarksville, Tennessee  37043
Fallon Clinic Worcester, Massachusetts  01605
Coastal Bend Cancer Center Corpus Christi, Texas  78404
Oncology Hematology Care Cincinnati, Ohio  45242
Watson Clinic Center for Cancer Care and Research Lakeland, Florida  33805
Oncology Hematology Associates of SW Indiana Evansville, Indiana  47714
Providence Medical Group Terre Haute, Indiana  47802
Hematology Oncology Associates of Northern NJ Morristown, New Jersey  07960
Chattanooga Oncology Hematology Associates Chattanooga, Tennessee  37404
Hematology Oncology of Indiana Indianapolis, Indiana  46260
Associates in Hematology Oncology Chattanooga, Tennessee  37404
Medical College of Georgia Cancer Specialists Augusta, Georgia  30912
Florida Cancer Care Davie, Florida  33328
Mid Ohio Oncology/Hematology, Inc./ The Mark H. Zangmeister Center Columbus, Ohio  43219
Lynn Cancer Institute Boca Raton, Florida  33428
Center for Cancer and Blood Disorders Ft. Worth, Texas  76104
Weinberg Cancer Institute at Franklin Square Baltimore, Maryland  21237
Cancer Center of Huntsville Huntsville, Alabama  35801
University of Southern Alabama Mobile, Alabama  36604
New Hope Cancer and Research Institute Pomona, California  91767
Eastern Connecticut Hematology Oncology Norwich, Connecticut  06360
Aventura Medical Center Aventura, Florida  33180
Piedmont Healthcare Atlanta, Georgia  30309
Emory/Winship Cancer Institute Atlanta, Georgia  30322
Suburban Hem Onc Lawrenceville, Georgia  30045
Mid-Illinois Hematology & Oncology Normal, Illinois  61761
Hematology Oncology of the North Shore Skokie, Illinois  60076
Cotton O'Neil Cancer Center Topeka, Kansas  66606
Fairview Medical Oncology Clinic Edina, Minnesota  55436
St. John's Clinic Springfield, Missouri  65804
St. Clare's Hospital Oncology and Hematology Denville, New Jersey  07834
Southern Oncology and Hematology South Jersey Healthcare - RMC Vineland, New Jersey  08360
Southern Oncology and Hematology Vineland, New Jersey  08360
Hematology/Oncology Inc Elyria, Ohio  44035
Hickman Cancer Center (Flower Hospital) Sylvania, Ohio  43560
Bux-Mont Oncology, Fox Chase Cancer Center Rockledge, Pennsylvania  18960
Lowcountry Hematology Oncology Mt. Pleasant, South Carolina  29464
Medical Oncology Methodist Hospital Houston, Texas  77030