Overview

This trial is active, not recruiting.

Condition breast cancer
Treatments doxorubicin, cyclophosphamide, ixabepilone (ixempra), paclitaxel (taxol)
Phase phase 3
Sponsor SCRI Development Innovations, LLC
Collaborator Bristol-Myers Squibb
Start date January 2009
End date December 2015
Trial size 614 participants
Trial identifier NCT00789581, SCRI BRE 145, TITAN

Summary

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

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(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.
doxorubicin Adriamycin
Doxorubicin 60 mg/m2
cyclophosphamide Endoxan
Cyclophosphamide 600 mg/m2
ixabepilone (ixempra) Ixempra
Ixabepilone 40 mg/m2
(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.
doxorubicin Adriamycin
Doxorubicin 60 mg/m2
cyclophosphamide Endoxan
Cyclophosphamide 600 mg/m2
paclitaxel (taxol) Taxol
Paclitaxel 80 mg/m2

Primary Outcomes

Measure
Disease Free Survival
time frame: 5.25 years

Secondary Outcomes

Measure
Overall Survival
time frame: 5.25 years
Number of treatment-emergent adverse events as a measure of safety.
time frame: evry 21 days for duration of treatment

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria

  • Female patients greater than or equal to18 years of age.
  • Histologically confirmed invasive unilateral breast cancer (regardless of histology).
  • 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).
  • 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.
  • Multicentric and multifocal invasive breast cancer is eligible if loco-regional surgery has been completed as described above.
  • 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.
  • 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).
  • Estrogen receptor negative (<10% staining by IHC for estrogen receptor).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Patient must be <= 84 days from having completed definitive primary breast surgery (either lumpectomy or mastectomy).
  • 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.
  • Adequate hematologic function, defined by:
    • Absolute neutrophil count (ANC) >1500/mm3
    • Platelet count >=100,000/mm3
    • Hemoglobin >9 g/dL
  • 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).
  • Adequate renal function, defined by:
    • Serum creatinine <=1.5 x ULN
  • 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.
  • 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).
  • 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).
  • 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.
  • 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.
  • Patient must be accessible for treatment and follow-up.
  • 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.
  • All patients must be able to understand the investigational nature of the study and give written informed consent prior to study entry.

Exclusion Criteria

  • Women who are pregnant or breastfeeding.
  • 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.
  • Any evidence or suspicion of metastatic disease other than ipsilateral axillary lymph nodes.
  • Any tumor >=T4 (cutaneous invasion, deep adherence, inflammatory breast cancer).
  • Previous anthracycline chemotherapy.
  • Concurrent use of CYP3A4 inhibitors from 72 hours prior to initiation of study treatment until the end of treatment with ixabepilone.
  • Previous treatment for this breast cancer (including neoadjuvant chemotherapy).
  • 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).
  • Peripheral neuropathy of > grade 1 per NCI CTCAE v3.0.
  • 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.
  • History of hypersensitivity to CremophorEL (polyoxyethylated castor oil) or a drug formulated in CremophorEL such as paclitaxel.
  • Use of any investigational agent within 30 days of administration of the first dose of study drug.
  • Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
  • 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.
  • Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
  • Inability to comply with study and/or follow-up procedures.

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by SCRI Development Innovations, LLC.