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

NCT ID: NCT00789581

Last Updated: 2017-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 614 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2016-11-30

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Doxorubicin

Intervention Type: DRUG

Doxorubicin 60 mg/m2

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide 600 mg/m2

Ixabepilone (Ixempra)

Intervention Type: DRUG

Ixabepilone 40 mg/m2

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.

Group Type: ACTIVE_COMPARATOR

Doxorubicin

Intervention Type: DRUG

Doxorubicin 60 mg/m2

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide 600 mg/m2

Paclitaxel (Taxol)

Intervention Type: DRUG

Paclitaxel 80 mg/m2

Interventions

Doxorubicin

Doxorubicin 60 mg/m2

Intervention Type: DRUG

Cyclophosphamide

Cyclophosphamide 600 mg/m2

Intervention Type: DRUG

Ixabepilone (Ixempra)

Ixabepilone 40 mg/m2

Intervention Type: DRUG

Paclitaxel (Taxol)

Paclitaxel 80 mg/m2

Intervention Type: DRUG

Other Intervention Names

Adriamycin; hydroxydaunorubicin; Adriamycin PFS; Adriamycin RDF; Rubex; Endoxan; Cytoxan; Neosar; Procytox; Revimmune; Cytophosphane; Ixempra; azaepothilone B; BMS-247550; Taxol

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

SCRI Development Innovations, LLC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Denise A Yardley, M.D.

Role: STUDY_CHAIR

SCRI Development Innovations, LLC

Locations

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

Florida Cancer Care

Davie, Florida, United States

Holy Cross Hospital

Fort Lauderdale, Florida, United States

Florida Cancer Specialists

Fort Myers, Florida, United States

Memorial Regional Cancer Center

Hollywood, Florida, United States

Integrated Community Oncology Network

Jacksonville, Florida, United States

Watson Clinic Center for Cancer Care and Research

Lakeland, Florida, United States

Space Coast Medical Associates

Titusville, Florida, United States

Piedmont Healthcare

Atlanta, Georgia, United States

Emory/Winship Cancer Institute

Atlanta, Georgia, United States

Augusta Oncology Associates

Augusta, Georgia, United States

Medical Oncology Associates of Augusta

Augusta, Georgia, United States

Medical College of Georgia Cancer Specialists

Augusta, Georgia, United States

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Suburban Hem Onc

Lawrenceville, Georgia, United States

Mid-Illinois Hematology & Oncology

Normal, Illinois, United States

Hematology Oncology of the North Shore

Skokie, Illinois, United States

Oncology Hematology Associates of SW Indiana

Evansville, Indiana, United States

Hematology Oncology of Indiana

Indianapolis, Indiana, United States

Providence Medical Group

Terre Haute, Indiana, United States

Kansas City Cancer Centers

Overland Park, Kansas, United States

Cotton O'Neil Cancer Center

Topeka, Kansas, United States

Consultants in Blood Disorders and Cancer

Louisville, Kentucky, United States

Baton Rouge General Medical Center

Baton Rouge, Louisiana, United States

Mercy Hospital

Portland, Maine, United States

Weinberg Cancer Institute at Franklin Square

Baltimore, Maryland, United States

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States

Fallon Clinic

Worcester, Massachusetts, United States

Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, United States

Fairview Medical Oncology Clinic

Edina, Minnesota, United States

St. Louis Cancer Care

Chesterfield, Missouri, United States

Research Medical Center

Kansas City, Missouri, United States

St. John's Clinic

Springfield, Missouri, United States

Methodist Cancer Center

Omaha, Nebraska, United States

St. Clare's Hospital Oncology and Hematology

Denville, New Jersey, United States

Hematology Oncology Associates of Northern NJ

Morristown, New Jersey, United States

Southern Oncology and Hematology

Vineland, New Jersey, United States

New Mexico Oncology Hematology Consultants

Albuquerque, New Mexico, United States

Alamance Regional Medical Center

Burlington, North Carolina, United States

Oncology Hematology Care

Cincinnati, Ohio, United States

Mid Ohio Oncology/Hematology, Inc./ The Mark H. Zangmeister Center

Columbus, Ohio, United States

Hematology/Oncology Inc

Elyria, Ohio, United States

Hickman Cancer Center (Flower Hospital)

Sylvania, Ohio, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Bux-Mont Oncology, Fox Chase Cancer Center

Rockledge, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

South Carolina Oncology Associates, PA

Columbia, South Carolina, United States

Lowcountry Hematology Oncology

Mt. Pleasant, 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

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, United States

Family Cancer Center

Collierville, Tennessee, United States

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Coastal Bend Cancer Center

Corpus Christi, Texas, United States

Center for Cancer and Blood Disorders

Fort Worth, Texas, United States

Medical Oncology Methodist Hospital

Houston, Texas, United States

South Texas Oncology and Hematology

San Antonio, 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

Countries

United States; Puerto Rico

References

Yardley DA, Arrowsmith ER, Daniel BR, Eakle J, Brufsky A, Drosick DR, Kudrik F, Bosserman LD, Keaton MR, Goble SA, Bubis JA, Priego VM, Pendergrass K, Manalo Y, Bury M, Gravenor DS, Rodriguez GI, Inhorn RC, Young RR, Harwin WN, Silver C, Hainsworth JD, Burris HA 3rd. TITAN: phase III study of doxorubicin/cyclophosphamide followed by ixabepilone or paclitaxel in early-stage triple-negative breast cancer. Breast Cancer Res Treat. 2017 Aug;164(3):649-658. doi: 10.1007/s10549-017-4285-6. Epub 2017 May 15.

Reference Type: BACKGROUND

PMID: 28508185 (View on PubMed)

Other Identifiers

TITAN

Identifier Type: -

Identifier Source: secondary_id

SCRI BRE 145

Identifier Type: -

Identifier Source: org_study_id