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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00789581
Recruitment Status : Completed
First Posted : November 13, 2008
Results First Posted : April 12, 2017
Last Update Posted : July 2, 2017
Bristol-Myers Squibb
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Brief Summary:
This is a randomized, Phase III, open-label, multicenter study.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Doxorubicin Drug: Cyclophosphamide Drug: Ixabepilone (Ixempra) Drug: Paclitaxel (Taxol) Phase 3

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 614 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase III Study of Doxorubicin/Cyclophosphamide (AC) Followed by Ixabepilone vs. AC Followed by Paclitaxel in Patients With Triple-Negative Early-Stage Breast Cancer
Study Start Date : December 2008
Actual Primary Completion Date : December 2015
Actual Study Completion Date : November 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: 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.
Drug: 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

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.
Drug: 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: Paclitaxel (Taxol)
Paclitaxel 80 mg/m2
Other Name: Taxol

Primary Outcome Measures :
  1. Disease-free Survival [ Time Frame: 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 :
  1. Overall Survival [ Time Frame: 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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Female patients greater than or equal to18 years of age.
  2. Histologically confirmed invasive unilateral breast cancer (regardless of


  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


    • 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


    • 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


  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00789581

  Show 70 Study Locations
Sponsors and Collaborators
SCRI Development Innovations, LLC
Bristol-Myers Squibb
Study Chair: Denise A Yardley, M.D. SCRI Development Innovations, LLC

Responsible Party: SCRI Development Innovations, LLC Identifier: NCT00789581     History of Changes
Other Study ID Numbers: SCRI BRE 145
First Posted: November 13, 2008    Key Record Dates
Results First Posted: April 12, 2017
Last Update Posted: July 2, 2017
Last Verified: June 2017

Keywords provided by SCRI Development Innovations, LLC:
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors