Abstract OT3-02-05: Phase II study of eribulin in combination with gemcitabine for the treatment of patients with locally advanced or metastatic triple negative breast cancer. ERIGE Trial on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC)
Authors: Musolino A , Caldara A , Montemurro F , Frassoldati A , Cavazzini G , Cavanna L , Todeschini R , Camisa R , Tognetto M , Pinto C 
Published: May 2016

Abstract
Background: There are no well-established chemotherapy regimens for metastatic triple negative breast cancer. The combination of a microtubule inhibitor (eribulin) with a nucleoside analog (gemcitabine) may synergistically induce tumor cell death, especially in tumors like triple negative breast cancers characterized by high cell proliferation, aggressive tumor behavior, and chemo-resistance.
Trial design: This is an open-label, national multicenter phase 2 study evaluating the combination of eribulin (0.88 mg/m2) plus gemcitabine (1000 mg/m2) on day 1 and 8, q21 as either first- or second-line treatment of locally advanced or metastatic triple negative breast cancer (TNBC). A prospective, molecular correlative study is being carried out on germinal DNA of study population.
Eligibility criteria: Patients must have locally advanced or metastatic breast cancer with estrogen receptor-negative (ER &lt; 1%), progesterone receptor-negative (PR &lt; 1%), and human epidermal growth factor receptor 2-negative (Her2-) (0, 1+) or, e.g. in HER2 2+ cases, fluorescent in situ hybridization (FISH) &lt; ratio of 1.8, status. Previous chemotherapy including an anthracycline and a taxane (unless one or both were clinically contraindicated) is mandatory. Up to one prior chemotherapy regimen for metastatic disease is permitted, with the exception of treatment with eribulin and gemcitabine. Patients must have: Measurable disease; Eastern Cooperative Oncology Group (ECOG) performance status 0-2; adequate bone marrow reserve, liver and renal function.
Specific aims: The main objective of this trial is to evaluate the activity of eribulin plus gemcitabine in terms of overall response rate (ORR; RECIST 1.1). Secondary end-points are: Feasibiliy, safety (CTC-AE V4.0), progression-free and overall survival. The molecular correlative study aim is to assess the role of germinal DNA polymorphisms and BRCA mutations in predicting efficacy and toxicity with the combination regimen.
Statistical methods: The primary endpoint is the ORR. The study is being carried out according to Optimal Simon's two stage design. We chose the lower activity (p0) of 0.20 and target activity level (p1) of 0.35. A total of 83 (37 in the first stage, 46 in the second one) assessable patients will be needed to guarantee 90% power under a α-level of 5%. Genotypic correlations with clinical responses and toxicities will be performed using a two-tailed Fisher's exact test. A logistic regression analysis including patients' genotypes will be used to identify independent prognostic variables influencing both clinical responses and toxicities.
Present accrual and target accrual: A total of 83 eligible patients will be enrolled from multiple institutions. To date (June 09, 2015), the first stage has been closed with 37 patients enrolled. The second stage is now recruiting 46 additional patients.
Citation Format: Musolino A, Caldara A, Montemurro F, Frassoldati A, Cavazzini G, Cavanna L, Todeschini R, Camisa R, Tognetto M, Pinto C. Phase II study of eribulin in combination with gemcitabine for the treatment of patients with locally advanced or metastatic triple negative breast cancer. ERIGE Trial on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC). [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 OT3-02-05.