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

NCT01534455 | Terminated Phase 2 DMC

• 2 other identifiers: GBG 642010-023237-37
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Breast Cancer

Keywords

German Breast Group; GBG Forschungs GmbH; GBG; GBG 64; E-VITA; Breast Cancer; Metastatic Breast Cancer; Eribulin; Lapatinib; Halaven; Tyverb

Outcome Measures

Primary Outcomes (3)

• Time to Progression (TTP)

  3 years

• Safety of the Therapy

  Number and percentage of participants who comply and tolerate the Therapy.

  3 years

• Toxicity of Therapy

  Number and percentage of participants with Adverse Events (any Grade and Grade 3/4).

  3 years

Secondary Outcomes (4)

• Objective Response Rate

  3 years

• Overall Clinical Benefit Rate

  3 Years

• Overall Survival

  3 Years

• Assess PI3K mutation, PTEN expression and c-myc (Biomarkers) on primary tumor

  3 Years

Study Arms (2)

Lapatinib + 1,23 mg Eribulin

EXPERIMENTAL

Drug: Lapatinib + 1,23 mg Eribulin

Lapatinib + 1,76 mg Eribulin

EXPERIMENTAL

Drug: Lapatinib + 1,76 mg Eribulin

Interventions

Lapatinib + 1,23 mg Eribulin DRUG

Lapatinib 1000 mg/day + Eribulin 1,23 mg/m2 i.v. on day 1 and 8, q21

Lapatinib + 1,23 mg Eribulin

Lapatinib + 1,76 mg Eribulin DRUG

Lapatinib 1000 mg/day + Eribulin 1,23 mg/m2 i.v. on day 1 and 8, q21

Lapatinib + 1,76 mg Eribulin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
• Complete baseline documentation must be submitted via the web-based data collection system MedCODES® to the GBG Forschungs GmbH.
• Histological confirmed carcinoma of the breast with over-expression of HER2 (IHC3+ or FISH pos., according to current guidelines of AGO). Every effort should be made to make paraffin embedded tissue or slides from the original tumor and/or from metastatic tissue available for confirmation of diagnosis and additional translational research.
• Locally advanced or metastatic stage of disease not suitable for surgery or radiotherapy alone.
• Patients must have either measurable or non-measurable target lesions according to RECIST criteria. Complete staging work-up within 4 weeks prior to registration. All patients must have chest X-ray (PA and lateral), abdominal ultrasound or CT scan or MRI, and bone scan. In case of positive bone scan, bone X-ray is mandatory. Other tests may be performed as clinically indicated.
• The following previous systemic treatments are eligible:
• Previous treatment with trastuzumab either as (neo)adjuvant treatment for early breast cancer and/or first and/or second line treatment for metastatic breast cancer,
• adjuvant and up to 2 chemotherapy regimen for metastatic breast cancer,
• if previous chemotherapy regimen were anthracycline based, the maximum cumulative dose of prior anthracycline therapy must not exceed 360 mg/m² for doxorubicin and 720 mg/m² for epirubicin,
• adjuvant endocrine therapy,
• palliative endocrine treatments,
• treatment with bisphosphonates (adjuvant and/or palliative),
• at least 4 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation field or there must be pathologic proof of progressive disease. 7. Age \>18 years. 8. ECOG performance status 0-2. 9. Laboratory requirements:
• Absolute neutrophil count ≥ 1500 cells/ul,
• hemoglobin ≥ 10.0 g/dL (hemoglobin \<10.0 g/dL is acceptable if it is corrected by growth factor or transfusion),

You may not qualify if:

• Known hypersensitivity reaction to the compounds or incorporated substances (e.g. halichondrin B and/or halichondrin B chemical derivative).
• Patients who have received eribulin or lapatinib before.
• Concurrent immunotherapy or hormonal therapy (anti-hormonal, contraceptive and/or replacement therapy). Bisphosphonates may be continued.
• Life expectancy of less than 3 months.
• Parenchymal brain metastases, unless adequately treated by neurosurgery, radiotherapy, radiosurgery or a combination.
• Any ongoing toxicity from prior anti-cancer therapy that is grade \>1 and/or that is progressing in severity, except alopecia or for stable sensory neuropathy Grade 2.
• Known or suspected congestive heart failure (\>NYHA I) and/or coronary heart disease, angina pectoris requiring anti-anginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, un- or poorly controlled arterial hypertension (i.e. BP \>150/100 mmHg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease.
• Currently active infection.
• History of other malignancies within the last 5 years which could affect the diagnosis, assessment or prognosis of metastatic breast cancer.
• Malabsorption syndrome or insufficient gastrointestinal function, preexisting diagnosis of ulcerative colitis.
• Concurrent treatment with other experimental drugs; participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.
• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.

Sponsors & Collaborators

• GBG Forschungs GmbH: lead

Study Sites (1)

Klinikum der Otto-v.-Guericke-Universität Frauenklinik

Magdeburg, 39108, Germany

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Joachim Bischoff, MD

  University Women's Hospital Magdeburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2012
• First Posted: February 16, 2012
• Study Start: February 1, 2012
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: February 10, 2016

Record last verified: 2016-02

Locations

DE (1)