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

S

SCRI Development Innovations

Status and phase

Completed
Phase 3

Conditions

Breast Cancer

Treatments

Drug: Paclitaxel (Taxol)
Drug: Doxorubicin
Drug: Ixabepilone (Ixempra)
Drug: Cyclophosphamide

Study type

Interventional

Funder types

Other
Industry

Identifiers

NCT00789581
SCRI BRE 145
TITAN

Details and patient eligibility

About

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

Full 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.

Enrollment

614 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

614 participants in 2 patient groups

Doxorubicin/cyclophosphamide, ixabepilone
Experimental group
Description:
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.
Treatment:
Drug: Cyclophosphamide
Drug: Ixabepilone (Ixempra)
Drug: Doxorubicin
Doxorubicin/cyclophosphamide, paclitaxel
Active Comparator group
Description:
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.
Treatment:
Drug: Cyclophosphamide
Drug: Paclitaxel (Taxol)
Drug: Doxorubicin

Trial contacts and locations

70

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Data sourced from clinicaltrials.gov

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