Abstract OT3-1-02: The SNAP trial: Schedules of nab-paclitaxel in metastatic breast cancer, International breast cancer study group (IBCSG 42-12) and breast International group (BIG 2-12)

Abstract

Abstract Background The SNAP trial aims to improve the tolerability of prolonged chemotherapy administration by studying alternative treatment schedules, while preserving and possibly improving treatment efficacy. Trial Design Randomized phase II study (1:1:1 randomization) evaluates each of 3 treatment arms versus a historical reference to determine whether any of the three are worthy of further investigation. All patients will begin with 3 cycles of nab-Paclitaxel 150 mg/m2 days 1,8,15 every 28 days. Maintenance nab-Paclitaxel will be given every 28 days until disease progression: (A) 150 mg/m2 days 1, 15, (B) 100 mg/m2 days 1, 8, 15, (C) 75 mg/m2 days 1, 8, 15, 22. Major Eligibility Criteria • Histologically or cytologically confirmed HER2-negative metastatic (stage IV) breast cancer • No prior chemotherapy for metastatic breast cancer • Measurable or non-measurable, but radiologically evaluable, disease according to RECIST 1.1 criteria • Either ER-positive or ER-negative disease. Patients with ER-positive disease must be endocrine resistant, defined as having failed at least one prior endocrine therapy for breast cancer, or must be candidates for first-line chemotherapy • Normal hematologic, renal, liver and cardiac functions • No peripheral neuropathy grade 2 or higher Specific Aim To evaluate the efficacy of three different schedules of nab-Paclitaxel for first-line treatment of metastatic breast cancer, measured by progression-free survival (PFS), using the historical reference of PFS for docetaxel. Statistical Methods The primary efficacy endpoint of PFS will be evaluated among each of the three treatment arms separately, in three independent tests, and compared to the historic PFS of first-line docetaxel. Assuming the median PFS of docetaxel is 7 months and the median PFS of a new regimen is 10 months, with 76 patients in each arm, and an accrual rate of 8 patients per month for an accrual period of 30 months plus 12 months additional follow-up, the study will have 88% power to detect an improvement in PFS in a new regimen relative to docetaxel, using a one-sample log-rank test at the one-sided significance level of 0.05. The target number of events per group is 63. The sample size of 80 patients per arm assumes a 5% drop out rate. Accrual Target: 240; Present: 1 (June 1, 2013) Related Research Translational research will investigate the prognostic role of putative markers SPARC and caveolin determined in FFPE tumor tissue from primary surgery and, if available, from metastatic biopsy. Material will be banked centrally. Quality-of-life assessments will be conducted to explore the change in QL over time until treatment discontinuation by LASA scales for physical well-being, mood, coping effort, overall treatment burden, appetite, tiredness, hair loss and feeling sick (nausea/vomiting). Sensory neuropathy will be assessed by the 4-item subscale of the FACT/GOG-Ntx. The SNAP trial is a collaboration through the Breast International Group (BIG). For more information about SNAP contact Dr. Rudolf Maibach, IBCSG Coordinating Center, Bern, Switzerland, rudolf.maibach@ibcsg.org, or the Trial Coordinators at ibcsg42_SNAP@fstrf.org. Pharmaceutical Support Celgene; Sponsor: IBCSG. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-1-02.