ER, PgR, and HER2 negative (triple negative) metastatic breast cancer MedDRA version: 18.0 Level: HLT Classification code 10006289 Term: Benign and malignant breast neoplasms System Organ Class: 100000004872 MedDRA version: 18.0 Level: PT Classification code 10055113 Term: Breast cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Abraxane
Product Code: nab-paclitaxel, ABI-007
Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Current Sponsor code: ABI-00
Sponsors
Abraxis BioScience, LLC, a wholly-owned subsidiary of Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria are met: 1. Female subjects, age = 18 years at the time informed consent is signed 2. Pathologically confirmed adenocarcinoma of the breast 3. Pathologically confirmed as triple negative, source documented, defined as both of the following a. Estrogen Receptor (ER) and Progesterone Receptor (PgR) negative: 60 mL/min (by Cockroft-Gault) 15. Females of child-bearing potential [defined as a sexually mature women who (1) have not undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time during
Exclusion criteria
Exclusion criteria: 1. Male subjects. 2. Concurrent chemotherapy or any other anti-tumor therapy for breast cancer. Prior immunotherapy & monoclonal antibody therapy are acceptable. 3. Subjects who received prior cytotoxic chemotherapy after incomplete resection of locoregional recurrent disease. 4. History of, or known current evidence of brain metastasis, including leptomeningeal involvement. 5. Subjects with bone as the only site of metastatic disease 6. Subjects with regional lymph node as the only site of metastatic disease as per AJCC TNM 7. Serious intercurrent medical or psychiatric illness, including serious active infection 8. History of class II-IV congestive heart failure or myocardial infarction within 6 months of randomization. 9. History of other primary malignancy in the last 5 years. Subjects with prior breast cancer history are eligible, however the most recently obtained biopsy must demonstrate triple negative disease (source documented). Subjects with prior history of in situ cancer or basal or localized squamous cell skin cancer are eligible. 10. Subjects with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple uncontrolled or unstable allergies which, in the opinion of the investigator, may lead to serious complications. 11. Peripheral neuropathy Grade = 2 by NCI CTCAE v4.0 12. Subjects who have received an investigational product within the previous 4 weeks prior to randomization 13. Subject is currently enrolled, or will enroll in a different clinical study in which investigational therapeutic procedures are performed or investigational therapies are administered while participating in this study 14. Pregnant or nursing women 15. Subjects with prior hypersensitivity to nab-paclitaxel, gemcitabine, carboplatin or any other platin, or nucleoside analogue agents 16. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study 17. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if she were to participate in the study 18. Any condition that confounds the ability to interpret data from the study 19. History of seropositive human immunodeficiency virus (HIV) 20. Subjects who are receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the investigator, increase the risk of serious neutropenic complications
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Phase 2: evaluate the benefit and risk profiles of the two nab-paclitaxel experimental arms and identify the nab-paclitaxel combination that will be used in the Phase 3. - Phase 3: compare the progression-free survival (PFS) of nab-paclitaxel plus carboplatin to gemcitabine/carboplatin in subjects with TNMBC, as assessed by independent blinded radiologist(s) using RECIST 1.1 guidelines.;Secondary Objective: - Phase 2: ? safety ? investigator-determined progression free survival (PFS) ? investigator-determined overall response rate (ORR) ? Overall survival (OS) - Phase 3: ? Compare safety and tolerability of each treatment regimen ? Compare Overall Response Rate (ORR), determined by independent blinded radiologist(s) ? Compare Overall Survival (OS) ? Compare Disease Control Rate (CR, PR and SD = 16 weeks) ? Compare Duration of Response;Primary end point(s): Phase II: Progression-Free Survival (PFS) based on investigator assessment of response using RECIST 1.1 guidelines. Phase III: Progression-Free Survival (PFS) based on an independent blinded radiologist(s) assessment using RECIST 1.1 guidelines.;Timepoint(s) of evaluation of this end point: - in phase II: when approximately 144 PFS events have ocurred - in phase III: when 330 PFS events or 217 deaths have ocurred, whichever is later | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - phase II: ? Efficacy: Overall Response Rate (ORR), investigator-determined, using RECIST 1.1 guidelines; percentage of subjects who initiated Cycle 6; overall Survival ? Safety: Incidence/Grade of TEAEs, serious adverse events (SAEs), laboratory abnormalities; incidence of subjects experiencing dose modifications (dose interruptions and reductions); percentage of subjects who discontinued for adverse event - Phase III: key secondary endpoints: ORR with a confirmed complete or partial response; OS; others: efficacy (investigator assessment of PFS; disease control rate; duration of response in subjects with objective CR or PR), safety (incidence of TEAEs, SAEs, laboratory abnormalities);Timepoint(s) of evaluation of this end point: phase II: efficacy and safety at cut-off date of follow-up period phase III: efficacy and safety at cut-off date of follow-up period; final analysis of overall survival after approximately 309 deaths | — |
Countries
Australia, Austria, Brazil, Canada, France, Germany, Greece, Italy, Japan, Portugal, Spain, United Kingdom, United States
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed