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

Phase 3

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Ixabepilone (Ixempra); Drug: Paclitaxel (Taxol)

• 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.

Study Timeline

• Study First Submitted: 2008-11-11
• Study First Submitted QC: 2008-11-12
• Study First Posted: 2008-11-13
• Study Start: 2008-12
• Primary Completion: 2015-12
• Study Completion: 2016-11
• Results First Submitted: 2016-11-07
• Results First Submitted QC: 2017-03-01
• Results First Posted: 2017-04-12
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-13
• Last Update Posted: 2017-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 614

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.

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)

Chattanooga Oncology Hematology Associates; 🇺🇸 Chattanooga, Tennessee, United States

Mercy Hospital; 🇺🇸 Portland, Maine, United States

Kansas City Cancer Centers; 🇺🇸 Overland Park, Kansas, United States

Piedmont Healthcare; 🇺🇸 Atlanta, Georgia, United States

Emory/Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Hematology Oncology of Indiana; 🇺🇸 Indianapolis, Indiana, United States

Northeast Alabama Regional Medical Center; 🇺🇸 Anniston, Alabama, United States

Clearview Cancer Institute; 🇺🇸 Huntsville, Alabama, United States

Wilshire Oncology Medical Group; 🇺🇸 La Verne, California, United States

University of Southern Alabama; 🇺🇸 Mobile, Alabama, United States

New Hope Cancer and Research Institute; 🇺🇸 Pomona, California, United States

Aventura Medical Center; 🇺🇸 Aventura, Florida, United States

Lynn Cancer Institute; 🇺🇸 Boca Raton, Florida, United States

Holy Cross Hospital; 🇺🇸 Fort Lauderdale, Florida, United States

Memorial Regional Cancer Center; 🇺🇸 Hollywood, Florida, United States

Florida Cancer Specialists; 🇺🇸 Fort Myers, Florida, United States

Integrated Community Oncology Network; 🇺🇸 Jacksonville, Florida, United States

Space Coast Medical Associates; 🇺🇸 Titusville, Florida, United States

Watson Clinic Center for Cancer Care and Research; 🇺🇸 Lakeland, Florida, United States

Augusta Oncology Associates; 🇺🇸 Augusta, Georgia, United States

Medical Oncology Associates of Augusta; 🇺🇸 Augusta, Georgia, United States

Northeast Georgia Medical Center; 🇺🇸 Gainesville, Georgia, United States

Medical College of Georgia Cancer Specialists; 🇺🇸 Augusta, Georgia, United States

Mid-Illinois Hematology & Oncology; 🇺🇸 Normal, Illinois, United States

Suburban Hem Onc; 🇺🇸 Lawrenceville, Georgia, United States

Hematology Oncology of the North Shore; 🇺🇸 Skokie, Illinois, United States

Oncology Hematology Associates of SW Indiana; 🇺🇸 Evansville, Indiana, United States

Providence Medical Group; 🇺🇸 Terre Haute, Indiana, United States

Baton Rouge General Medical Center; 🇺🇸 Baton Rouge, Louisiana, United States

Weinberg Cancer Institute at Franklin Square; 🇺🇸 Baltimore, Maryland, United States

Grand Rapids Clinical Oncology Program; 🇺🇸 Grand Rapids, Michigan, United States

Center for Cancer and Blood Disorders; 🇺🇸 Fort Worth, Texas, United States

Fairview Medical Oncology Clinic; 🇺🇸 Edina, Minnesota, United States

St. Louis Cancer Care; 🇺🇸 Chesterfield, Missouri, United States

St. John's Clinic; 🇺🇸 Springfield, Missouri, United States

St. Clare's Hospital Oncology and Hematology; 🇺🇸 Denville, New Jersey, United States

New Mexico Oncology Hematology Consultants; 🇺🇸 Albuquerque, New Mexico, United States

Alamance Regional Medical Center; 🇺🇸 Burlington, North Carolina, United States

Hematology/Oncology Inc; 🇺🇸 Elyria, Ohio, United States

Mid Ohio Oncology/Hematology, Inc./ The Mark H. Zangmeister Center; 🇺🇸 Columbus, Ohio, United States

Hickman Cancer Center (Flower Hospital); 🇺🇸 Sylvania, Ohio, United States

Bux-Mont Oncology, Fox Chase Cancer Center; 🇺🇸 Rockledge, Pennsylvania, United States

South Carolina Oncology Associates, PA; 🇺🇸 Columbia, South Carolina, United States

Coastal Cancer Center; 🇺🇸 Myrtle Beach, South Carolina, United States

Spartanburg Regional Medical Center; 🇺🇸 Spartanburg, South Carolina, United States

Associates in Hematology Oncology; 🇺🇸 Chattanooga, Tennessee, United States

Medical Oncology Methodist Hospital; 🇺🇸 Houston, Texas, United States

Coastal Bend Cancer Center; 🇺🇸 Corpus Christi, Texas, United States

Peninsula Cancer Institute; 🇺🇸 Newport News, Virginia, United States

Virginia Cancer Institute; 🇺🇸 Richmond, Virginia, United States

San Juan Hospital; 🇵🇷 San Juan, Puerto Rico

Cotton O'Neil Cancer Center; 🇺🇸 Topeka, Kansas, United States

Oncology Hematology Care; 🇺🇸 Cincinnati, Ohio, United States

Tennessee Oncology, PLLC; 🇺🇸 Nashville, Tennessee, United States

South Texas Oncology and Hematology; 🇺🇸 San Antonio, Texas, United States

Cancer Center of Huntsville; 🇺🇸 Huntsville, Alabama, United States

Florida Cancer Care; 🇺🇸 Davie, Florida, United States

Consultants in Blood Disorders and Cancer; 🇺🇸 Louisville, Kentucky, United States

Research Medical Center; 🇺🇸 Kansas City, Missouri, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Fallon Clinic; 🇺🇸 Worcester, Massachusetts, United States

Eastern Connecticut Hematology Oncology; 🇺🇸 Norwich, Connecticut, United States

Hematology Oncology Associates of Northern NJ; 🇺🇸 Morristown, New Jersey, United States

Southern Oncology and Hematology; 🇺🇸 Vineland, New Jersey, United States

Northeast Arkansas Clinic; 🇺🇸 Jonesboro, Arkansas, United States

Lowcountry Hematology Oncology; 🇺🇸 Mount Pleasant, South Carolina, United States

Family Cancer Center; 🇺🇸 Collierville, Tennessee, United States

Methodist Cancer Center; 🇺🇸 Omaha, Nebraska, United States