Metastatic Breast CancerPhase 2NCT01534455
Efficacy and Tolerability of Eribulin Plus Lapatinib in Patients With Metastatic Breast Cancer (E-VITA)
A Phase 2 study testing Lapatinib + 1,23 mg Eribulin and Lapatinib + 1,76 mg Eribulin in people with Metastatic Breast Cancer, run by GBG Forschungs GmbH at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Lapatinib + 1,23 mg Eribulin and Lapatinib + 1,76 mg Eribulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteGermany
- Study dates
- Feb 2012to Mar 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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),
- platelet count ≥100,000 cells/ul,
- bilirubin <= 1.5x the upper limit of normal for the institution (ULN),
- elevation of transaminases and alkaline phosphatase < 2.5x ULN or <5x ULN for patients with liver metastases,
- creatinine <= 1.5 x ULN or creatinine-clearance > 40 ml/min (according to Cockroft Gault),
- negative pregnancy test (urine or serum) within 14 days prior to registration for all women of childbearing potential. 10. Normal cardiac ejection function as determined by cardiac ultrasound (LVEF above institutional normal range).
- 11. A female either of:
- Non-childbearing potential i.e., physiologically incapable of becoming pregnant because of history of hysterectomy, bilateral oophorectomy (ovarectomy), bilateral tubal ligation or postmenopausal status.
- Childbearing potential with a negative serum pregnancy test within 2 weeks prior to registration, preferably as close to the first dose as possible, and agrees to use adequate contraception. Acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:
- An intrauterine device with a documented failure rate of less than 1% per year.
- Vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female.
- Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product.
- Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide). 12. Female patients who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug.
- 13. Patients must be available and compliant for treatment and follow-up. Patients registered on this trial must be treated and followed up at the participating or a cooperating center.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Germany1 site
Klinikum der Otto-v.-Guericke-Universität Frauenklinik
Magdeburg, 39108
About this study
Official title: 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)
- 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.
Read the detailed description
Primary Objectives
- 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.
- To assess the safety and toxicity of both treatment arms.
Secondary Objectives
- To determine the objective response rate of both treatment arms.
- To determine the overall clinical benefit rate (CR + PR + SD >24 weeks) of both treatment arms.
- To determine overall survival in both treatment arms 3 years after 1st patient has been randomized.
- 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
- Being tested
- Lapatinib + 1,23 mg Eribulin, Lapatinib + 1,76 mg Eribulin
- Keywords
- German Breast Group, GBG Forschungs GmbH, GBG, GBG 64, E-VITA, Breast Cancer, Metastatic Breast Cancer, Eribulin, Lapatinib, Halaven, Tyverb
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lapatinib + 1,23 mg EribulinDrug
Lapatinib 1000 mg/day + Eribulin 1,23 mg/m2 i.v. on day 1 and 8, q21
Lapatinib + 1,76 mg EribulinDrug
Lapatinib 1000 mg/day + Eribulin 1,23 mg/m2 i.v. on day 1 and 8, q21
| Study group | Role | What they receive |
|---|---|---|
| Lapatinib + 1,23 mg Eribulin | Experimental | Not described Receives: Drug: Lapatinib + 1,23 mg Eribulin |
| Lapatinib + 1,76 mg Eribulin | Experimental | Not described Receives: Drug: Lapatinib + 1,76 mg Eribulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Progression (TTP)
Measured: 3 years
Safety of the Therapy
Number and percentage of participants who comply and tolerate the Therapy.
Measured: 3 years
Toxicity of Therapy
Number and percentage of participants with Adverse Events (any Grade and Grade 3/4).
Measured: 3 years
Secondary outcomes (4)
Objective Response Rate
Measured: 3 years
Overall Clinical Benefit Rate
Measured: 3 Years
Overall Survival
Measured: 3 Years
Assess PI3K mutation, PTEN expression and c-myc (Biomarkers) on primary tumor
Correlate the PI3K mutation, PTEN expression and c-myc found in the FFPE tissue samples with primary tumor characteristics.
Measured: 3 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2012 (estimated)
- Study startFeb 2012
- Primary completionMar 2015
- Study completionMar 2015
Why it stopped: very slow patient recruitment and concerns about the actuality of the study design
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- GBG Forschungs GmbH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joachim Bischoff, MD, Principal investigator, University Women's Hospital Magdeburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01534455
- Sponsor's protocol ID
- GBG 64
- Other IDs
- 2010-023237-37
- Status last verified
- Feb 2016
- First submitted
- 8 Feb 2012
- Last updated
- 10 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT01534455
- Acronym / sponsor ID
- GBG 64
- Conditions
- Metastatic Breast Cancer
- Keywords
- German Breast Group, GBG Forschungs GmbH, GBG, GBG 64, E-VITA, Breast Cancer, Metastatic Breast Cancer, Eribulin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: very slow patient recruitment and concerns about the actuality of the study design
- Enrolment
- 43 participants (actual)
- Lead sponsor
- GBG Forschungs GmbHUniversity, hospital or other
- Study start
- Feb 2012
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 16 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- 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
- 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.
- To assess the safety and toxicity of both treatment arms.
Secondary Objectives
- To determine the objective response rate of both treatment arms.
- To determine the overall clinical benefit rate (CR + PR + SD >24 weeks) of both treatment arms.
- To determine overall survival in both treatment arms 3 years after 1st patient has been randomized.
- To assess biomarkers like PI3K mutation, PTEN expression, c-myc on the primary tumor and correlate them with TTP in both treatment arms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lapatinib + 1,23 mg Eribulin | Experimental | Drug: Lapatinib + 1,23 mg Eribulin |
| Lapatinib + 1,76 mg Eribulin | Experimental | Drug: Lapatinib + 1,76 mg Eribulin |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lapatinib + 1,23 mg EribulinLapatinib 1000 mg/day + Eribulin 1,23 mg/m2 i.v. on day 1 and 8, q21 | Drug | Lapatinib + 1,23 mg Eribulin |
| Lapatinib + 1,76 mg EribulinLapatinib 1000 mg/day + Eribulin 1,23 mg/m2 i.v. on day 1 and 8, q21 | Drug | Lapatinib + 1,76 mg Eribulin |
Primary outcome
Time to Progression (TTP)
Time frame: 3 years
Safety of the Therapy
Time frame: 3 years
Number and percentage of participants who comply and tolerate the Therapy.
Toxicity of Therapy
Time frame: 3 years
Number and percentage of participants with Adverse Events (any Grade and Grade 3/4).
4 secondary outcomes
Objective Response Rate
Time frame: 3 years
Overall Clinical Benefit Rate
Time frame: 3 Years
Overall Survival
Time frame: 3 Years
Assess PI3K mutation, PTEN expression and c-myc (Biomarkers) on primary tumor
Time frame: 3 Years
Results and safety
The study was stopped early (reason given: very slow patient recruitment and concerns about the actuality of the study design). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joachim Bischoff, MD principal investigator
University Women's Hospital Magdeburg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lapatinib + 1,23 mg Eribulin and Lapatinib + 1,76 mg Eribulin in people with Metastatic Breast Cancer, run by GBG Forschungs GmbH at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: very slow patient recruitment and concerns about the actuality of the study design). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Progression (TTP) (time frame: 3 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2016.