Full Text View  
  Tabular View  
  Contacts and Locations  
  No Study Results Posted  
  Related Studies  
A Randomized Trial of Ixempra Versus Taxol in Adjuvant Therapy of Triple Negative Breast Cancer (TITAN)
This study is currently recruiting participants.
Verified by Sarah Cannon Research Institute, January 2009
Sponsors and Collaborators: Sarah Cannon Research Institute
SCRI Oncology Research Consortium
Bristol-Myers Squibb
Information provided by: Sarah Cannon Research Institute
ClinicalTrials.gov Identifier: NCT00789581
  Purpose

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


Condition Intervention Phase
Breast Cancer
Drug: Doxorubicin
Drug: Cyclophosphamide
Drug: Ixabepilone (Ixempra)
Drug: Paclitaxel (Taxol)
Phase III

Genetics Home Reference related topics: breast cancer
MedlinePlus related topics: Breast Cancer Cancer
Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Paclitaxel Ixabepilone
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
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

Further study details as provided by Sarah Cannon Research Institute:

Primary Outcome Measures:
  • 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. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To compare the overall survival. To assess the safety. To compare the DFS. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 1800
Study Start Date: January 2009
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Active Comparator
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
Drug: Cyclophosphamide
Cyclophosphamide 600 mg/m2
Drug: Ixabepilone (Ixempra)
Ixabepilone 40 mg/m2
2: Active Comparator
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
Drug: Cyclophosphamide
Cyclophosphamide 600 mg/m2
Drug: Paclitaxel (Taxol)
Paclitaxel 80 mg/m2

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 greater than or equal to 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00789581

Contacts
Contact: Denise A. Yardley, M.D. (615) 329-7274 dyardley@tnonc.com
Contact: Trials Info (615) 329-7274 trialsinfo@scresearch.net

Locations
United States, Florida
Florida Cancer Specialists Recruiting
Fort Myers, Florida, United States, 33901
Contact: Katie Goodman     239-274-9930     KatieG@flcancer.com    
United States, Tennessee
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37023
Sponsors and Collaborators
Sarah Cannon Research Institute
SCRI Oncology Research Consortium
Bristol-Myers Squibb
  More Information

Responsible Party: SCRI Oncology Research Consortium ( Denise Yardley, M.D. )
Study ID Numbers: SCRI BRE 145, TITAN
Study First Received: November 11, 2008
Last Updated: January 15, 2009
ClinicalTrials.gov Identifier: NCT00789581  
Health Authority: United States: Food and Drug Administration

Keywords provided by Sarah Cannon Research Institute:
Breast Cancer
Adjuvant
Doxorubicin
Cyclophosphamide
Paclitaxel
Ixabepilone
TITAN

Study placed in the following topic categories:
Skin Diseases
Paclitaxel
Epothilones
Breast Neoplasms
Cyclophosphamide
Doxorubicin
Breast Diseases

Additional relevant MeSH terms:
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Physiological Effects of Drugs
Antimitotic Agents
Antibiotics, Antineoplastic
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009