NCT01534455

Efficacy and Tolerability of Eribulin Plus Lapatinib in Patients With Metastatic Breast Cancer (E-VITA)

A Randomized Phase II Study to Determine the Efficacy and Tolerability of Two Doses of Eribulin Plus Lapatinib in Trastuzumab Pre-treated Patients With HER2-positive Metastatic Breast Cancer (E-VITA)

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: GBG Forschungs GmbH · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

* Lapatinib in combination with capecitabine has been approved for the treatment of women with HER-2-positive advanced breast cancer that have progressed after anthracycline-, taxane-, and trastuzumab-containing therapies. The use of this combination is limited by overlapping toxicity such as diarrhea and cutaneous side effects. * A significant number of patients receive today capecitabine with trastuzumab as first- or second-line treatment. Therefore, other combinations of lapatinib with less toxic cytotoxic agents are needed. * Eribulin mesylate (E7389) is a synthetic analog of Halichondrin B (HalB), a large polyether macrolide isolated from a marine sponge. Eribulin is a mechanistically unique antagonist of microtubule dynamics among tubulin-targeted agents, leading to inhibition of microtubule growth in the absence of effects on microtubule shortening, and formation of non- productive tubulin aggregates. * Eribulin mesylate at a dose of 1.4 mg/m² given on day 1, 8 every 3 weeks has shown better overall survival by 2.5 months compared to treatment of physicians choice in patients with locally advanced or metastatic breast cancer who were previously treated for 2-5 lines with anthracyclines, taxanes, and capecitabine (EMBRACE study). * The most frequently reported eribulin-related AEs were asthenia/fatigue (65%), alopecia (60%), neutropenia (60%), nausea (44%), anemia (28%), pyrexia (23%), leucopenia (22%), anorexia (21%), constipation (19%), vomiting (18%), and peripheral neuropathy (5.5%; only grade 3). Grade 4 neutropenia occurred in 32% of patients, and febrile neutropenia occurred in 5.5% of patients. The frequency of all other grade 3/4 AEs was less than 3%. This toxicity profile does not overlap with that of lapatinib. * There is uncertainty in how far a once every 3 week schedule of eribulin mesylate at a dose of 2.0 mg/m² would be better tolerated. Several phase II studies are currently conducted in various non-breast cancer indications to compare the d1+8 q d21 with a d1 q d21 schedule. * The aim of this randomized phase II study is to compare the efficacy and tolerability of two dose-schedules of eribulin plus lapatinib in HER2-positive breast cancer, pre-treated with trastuzumab in the adjuvant and/or metastatic setting.

Detailed description

Primary Objectives 1. To assess the time to progression (TTP) of eribulin at a dose of 1.23 mg/m² IV days 1+8, q 21 and eribulin given at a dose of 1.76 mg/m² IV day 1, q d21 both in combination with lapatinib. 2. To assess the safety and toxicity of both treatment arms. Secondary Objectives 1. To determine the objective response rate of both treatment arms. 2. To determine the overall clinical benefit rate (CR + PR + SD \>24 weeks) of both treatment arms. 3. To determine overall survival in both treatment arms 3 years after 1st patient has been randomized. 4. To assess biomarkers like PI3K mutation, PTEN expression, c-myc on the primary tumor and correlate them with TTP in both treatment arms.

Conditions

• Metastatic Breast Cancer

Interventions

Type	Name	Description
DRUG	Lapatinib + 1,23 mg Eribulin	Lapatinib 1000 mg/day + Eribulin 1,23 mg/m2 i.v. on day 1 and 8, q21
DRUG	Lapatinib + 1,76 mg Eribulin	Lapatinib 1000 mg/day + Eribulin 1,23 mg/m2 i.v. on day 1 and 8, q21

Timeline

• Start date: 2012-02-01
• Primary completion: 2015-03-01
• Completion: 2015-03-01
• First posted: 2012-02-16
• Last updated: 2016-02-10

Locations

1 site across 1 country: Germany