Phase 1 - Advanced and/or metastatic cancer Phase 2 - Advanced and/or metastatic breast cancer MedDRA version: 17.0 Level: LLT Classification code 10027477 Term: Metastatic carcinoma System Organ Class: 100000004864 MedDRA version: 17.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ
Conditions
Interventions
Trade Name: Halaven
Product Name: Eribulin mesylate
Product Code: E7389
Pharmaceutical Form: Solution for injection
Trade Name: Xeloda
Sponsors
Eisai Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects in Dose-escalation cohorts (Phase 1b): 1) Histologically or cytologically confirmed cancer that is advanced and/or metastatic 2) Resistant/refractory to approved therapies (defined as progressive disease during or within 6 months after the last anti-cancer therapy) or for whom single agent capecitabine at this dose level and schedule would be a reasonable treatment option in the opinion of the investigator 3) Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 2 4) For subjects that previously received capecitabine all capecitabine related toxicities must have completely resolved. Subjects in Dose-confirmation cohorts (Phase 2): 1) Histologically or cytologically confirmed carcinoma of the breast that is advanced and/or metastatic 2) Received up to three prior chemotherapy regimens in any setting (sequential neo-adjuvant/adjuvant treatment counting as one regimen) 3) Chemotherapy regimens must have included an anthracycline (unless anthracycline containing chemotherapy is inappropriate) and a taxane, either in combination or in separate regimens 4) No prior treatment with capecitabine in any setting 5) At least one lesion of = 1.5cm in longest diameter for non-lymph nodes and =1.5cm in shortest diameter for lymph nodes which is serially measurable according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 6) ECOG-PS 0 or 1 General inclusion criteria: 1) Adequate bone marrow function: absolute neutrophil count (ANC) = 1.5 x 109/L, hemoglobin = 10.0 g/dL (this may have been corrected by growth factor or transfusion), and platelet count = 100 x 109/L 2) Adequate liver function as evidenced by bilirubin = 1.5 times the upper limits of normal (ULN) and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) = 3 x ULN (in the case of liver metastases = 5 x ULN) 3) Adequate renal function as evidenced by calculated creatinine clearance = 50 mL/min as per the Cockcroft-Gault formula or radioisotope measurement Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 52 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: 1) Suspected dihydropyrimidine dehydrogenase (DPD) deficiency 2) Prior participation in an eribulin clinical study, even if not assigned to eribulin treatment 3) Pre-existing neuropathy > Grade 2 4) Subjects with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting study treatment. Any symptoms attributed to brain metastases must be stable for at least 4 weeks before starting study treatment; radiographic stability should be determined by comparing contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) brain scan performed during screening to a prior scan performed at least 4 weeks earlier. 5) Electrocardiogram (ECG) with QTc interval > 470 msec
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Dose-escalation cohorts (Phase 1b) • To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of eribulin when administered in combination with capecitabine in two different schedules in subjects with advanced and/or metastatic cancer Dose-confirmation cohort (Phase 2) • To evaluate the efficacy of the combination of eribulin and capecitabine when administered at the MTD (determined during Dose-escalation) in the chosen dosing schedule from Phase Ib in female subjects with advanced and/or metastatic breast cancer ; Secondary Objective: Secondary objectives • To evaluate the safety, tolerability and toxicity profile of eribulin when given in combination with capecitabine • To explore the pharmacokinetic (PK) profiles, including evaluating the potential for drug-drug interaction, of eribulin, capecitabine and capecitabine metabolites when eribulin and capecitabine are given in combination Exploratory objectives • To explore the pharmacokinetic/pharmacodynamic (PK/PD) relationship between the combination of eribulin and capecitabine with neutropenia ; Primary end point(s): Primary endpoint Dose-Escalation: A dose limiting toxicity (DLT) is defined as any of the following toxicities considered to be related to study treatment: • Neutropenia Grade 4 that lasts = 7 days • Neutropenia Grade 3 or 4 complicated by fever and/or infection (ANC 14 days • Failure to administer = 75% of the planned study drugs during Cycle 1 as a result of = Grade 2 treatment-related toxicity that constitutes an increase of = 2 grades from baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate the safety, tolerability and toxicity profile of eribulin when given in combination with capecitabine To explore the pharmacokinetic (PK) profiles, including evaluating the potential for drug-drug interaction, of eribulin, capecitabine and capecitabine metabolites when eribulin and capecitabine are given in combination ;Timepoint(s) of evaluation of this end point: At end of trial | — |
Countries
Bulgaria, Russian Federation, United Kingdom
Contacts
Public ContactMedical Information
Eisai Europe Ltd
Outcome results
None listed