Abstract OT3-02-04: Randomised phase II study evaluating, as first-line chemotherapy, single-agent oral vinorelbine administered with two different schedules in patients with hormone receptor positive, HER2-negative advanced breast cancer (TempoBreast-1 trial)
Authors: De la Haba J , Cazzaniga M , Freyer G , Costa L , Petru E , Bartsch R , Staroslawska E , de Almeida C , Villanova G , Cardoso F 
Published: May 2016

Abstract
Background: Single-agent chemotherapy (CT) is the standard treatment option for patients (pts) with hormone receptor (HR) positive disease progressing after previous hormone therapy (HT). Oral CT offers significant advantages over intravenous CT because of its greater convenience, its ease of administration and reduced need for hospitalisation. Metronomic CT could be considered as a multi-targeted therapy for advanced breast cancer, combining effects not only on tumour cells but also on their microenvironment by inhibiting angiogenesis and stimulating anticancer immune response. Metronomic oral vinorelbine (OV) has been evaluated in phase I and II trials setting 50 mg total dose three times per week as the reference dosing. This schedule provides promising efficacy results, combined with a potentially improved safety by reducing the risk of neutropenia. Weekly administration of oral vinorelbine is one of the standard chemotherapy options in the management of advanced breast cancer. This study will provide key clinical data regarding the optimal management of this pt population: HR positive and HER2-negative disease previously treated by a HT.
Trial design: In this open-label study, pts are randomised to receive (1 cycle = 3 weeks): OV 50 mg total dose three times weekly on Mondays, Wednesdays and Fridays (metronomic schedule) or OV 60 mg/m2/week (day 1, 8, 15) for the first cycle, then increased to 80 mg/m2/week from the second cycle in the absence of grade 3 or 4 toxicity (weekly schedule). Treatments are continued until disease progression, unacceptable toxicity or pt.'s refusal. Main eligibility criteria include: age ≥18 years, documented locally recurrent or metastatic disease previously untreated by CT, HR positive disease previously treated by at least one HT, HER2-negative disease, Karnofsky PS ≥70. Primary objective: disease-control rate. Secondary objectives: other efficacy parameters, evaluation of safety profiles of both arms and quality of life assessment. Statistical methods: the one-sample multiple testing procedure for phase II clinical trials described by Fleming is used. This procedure employs the standard single stage test procedure at the last one of 2 pre-specified testings, while both allowing for early termination (should extreme results be seen) and essentially preserving the size and power of the single stage procedure. 160 patients will be enrolled in this randomised phase II study (80 per treatment arm). Randomisation is stratified according to centre, prior taxane, prior everolimus and presence of visceral metastases. Study accrual is planned to start Q3 2015 with a duration of 24 months.
Citation Format: De la Haba J, Cazzaniga M, Freyer G, Costa L, Petru E, Bartsch R, Staroslawska E, de Almeida C, Villanova G, Cardoso F. Randomised phase II study evaluating, as first-line chemotherapy, single-agent oral vinorelbine administered with two different schedules in patients with hormone receptor positive, HER2-negative advanced breast cancer (TempoBreast-1 trial). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-02-04.