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Metastatic Breast CancerPhase 1/2NCT01323530

A Confirmation Study of Eribulin in Combination With Capecitabine

A Phase 1/2 study testing Eribulin mesylate and Capecitabine in people with Metastatic Breast Cancer, run by Eisai Limited at 10 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a Phase 1b/2, multi-center, open-label, dose escalation (in 2 different dosing schedules [1 and 2]) and dose-confirmation study of eribulin administered in combination with capecitabine. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
Eribulin mesylate and Capecitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
76 participants
Where
10 sitesin 3 countries
Study dates
26 Jan 2010to 13 Oct 2015
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects who meet all of the following criteria will be included in the study:
  • Dose-escalation cohorts (Phase 1b):
  • Histologically or cytologically confirmed cancer that is advanced and/or metastatic
  • 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
  • For subjects that previously received capecitabine, all capecitabine related toxicities must have completely resolved
  • Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L, hemoglobin greater than or equal to 10.0 g/dL (this may have been corrected by growth factor or transfusion), and platelet count greater than or equal to 100 x 10^9/L
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  • Adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the upper limit of normal (ULN) and alkaline phosphatase (AP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 x ULN (in the case of liver metastases less than or equal to 5 x ULN). In case AP is greater than 3 x ULN (in absence of liver metastases) or greater than 5 x ULN (in presence of liver metastases) AND subject also is known to have bone metastases, the liver specific AP must be separated from the total and used to assess the liver function instead of the total AP.
  • Adequate renal function as evidenced by calculated creatinine clearance greater than or equal to 50 mL/min as per the Cockcroft-Gault formula (Appendix 1) or radioisotope measurement.
  • Females of childbearing potential must have a negative urine or serum beta human chorionic gonadotropin (hCG) at Visit 1 (Screening) and prior to starting study drugs on Day 1. Female subjects of childbearing potential must agree to be abstinent or to use highly effective methods of contraception (e.g., condom + spermicide, condom + diaphragm with spermicide, intrauterine device (IUD), or have a vasectomized partner) having starting for at least one menstrual cycle prior to starting study drug(s) and throughout the entire study period and for 30 days (longer if appropriate) after the last dose of study drug. Those women using hormonal contraceptives must also be using an additional approved method of contraception (as described previously). Perimenopausal women must be amenorrheic for at least 12 months to be considered of nonchildbearing potential.
  • Male subjects who are not abstinent or have not undergone a successful vasectomy, who are partners of women of childbearing potential must use, or their partners must use, a highly affective method of contraception (e.g. condom + spermicide, condom + diaphragm with spermicide, IUD) starting for at least one menstrual cycle prior to starting study drug(s) and throughout the entire study period and for 30 days (longer if appropriate) after the last dose of study drug. Those with partners using hormonal contraceptives must also be using an additional approved method of contraception (as described previously)
  • Life expectancy of greater than 3 months
  • Willing and able to comply with all aspects of the protocol
  • Provide written informed consent
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) less than or equal to 2
  • Males and females, age greater than or equal to18 years
  • Dose-confirmation cohorts (Phase 2):
  • Histologically or cytologically confirmed carcinoma of the breast that is advanced and/or metastatic
  • Received up to three prior chemotherapy regimens in any setting (sequential neoadjuvant/ adjuvant treatment counting as one regimen)
  • Chemotherapy regimens must have included an anthracycline (unless anthracycline containing chemotherapy is inappropriate) and a taxane, either in combination or in separate regimens
  • No prior treatment with capecitabine in any setting
  • At least one lesion of greater than or equal to 1.5cm in longest diameter for non-lymph nodes and greater than or equal to 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 7
  • Adequate bone marrow function as evidenced by ANC greater than or equal to 1.5 x 10^9/L, hemoglobin greater than or equal to 10.0 g/dL (this may have been corrected by growth factor or transfusion), and platelet count greater than or equal to 100 x 10^9/L
  • Adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the upper limits of normal (ULN) and alkaline phosphatase (AP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal 3 x ULN (in the case of liver metastases less than or equal to 5 x ULN). In case AP is greater than 3 x ULN (in absence of liver metastases) or greater than 5 x ULN (in presence of liver metastases) AND subject also is known to have bone metastases, the liver specific AP must be separated from the total and used to assess the liver function instead of the total AP.
  • Adequate renal function as evidenced by calculated creatinine clearance greater than or equal to 50 mL/min as per the Cockcroft-Gault formula (Appendix 1) or radioisotope measurement.
  • Females of childbearing potential must have a negative urine or serum beta hCG at Visit 1 (Screening) and prior to starting study drugs on Day 1. Female subjects of childbearing potential must agree to be abstinent or to use highly effective methods of contraception (e.g., condom + spermicide, condom + diaphragm with spermicide, IUD, or have a vasectomized partner) having starting for at least one menstrual cycle prior to starting study drug(s) and throughout the entire study period and for 30 days (longer if appropriate) after the last dose of study drug. Those women using hormonal contraceptives must also be using an additional approved method of contraception (as described previously). Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential
  • Life expectancy of greater than 3 months
  • Willing and able to comply with all aspects of the protocol
  • ECOG-PS 0 or 1
  • Females, age greater than or equal to 18 years

Who cannot join

  • Subjects who meet any of the following criteria will be excluded from participation in the study:
  • Radiotherapy, chemotherapy, biological therapy or investigational agents within 4 weeks prior to the start of study treatment; subjects must have recovered from any previous therapy related toxicity to less than Grade 1 at study entry (except for stable sensory neuropathy less than or equal to Grade 2 and alopecia)
  • Treatment with mitomycin C or nitrosourea within 6 weeks prior to commencing on study treatment
  • Hormonal treatment within 2 weeks prior to start of study treatment (continued use of antiandrogens and/or gonadorelin analogues for treatment of prostate cancer permitted)
  • Prior participation in an eribulin clinical study, even if not assigned to eribulin treatment
  • Subject with hypersensitivity to halochondrin B and /or halochondrin B chemical derivates or capecitabine or any of the excipients
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  • Suspected dihydropyrimidine dehydrogenase (DPD) deficiency
  • Previous radiotherapy encompassing greater than 30% of marrow
  • Previous organ allograft requiring immunosuppression
  • 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 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
  • Meningeal carcinomatosis
  • Significant cardiovascular impairment (history of congestive heart failure greater than New York Heart Association [NYHA] grade II, unstable angina or myocardial infarction within the past 6 months, or serious cardiac arrhythmia)
  • Electrocardiogram (ECG) with QT interval corrected for heart rate (QTc) interval greater than 470 msec (as measured either by Bazett's or Fredericia's formula)
  • Pre-existing neuropathy greater than Grade 2
  • Anti-coagulant therapy with warfarin or related compounds, other than for line patency, that cannot be changed to heparin-based therapy for the duration of the study
  • Subjects with known positive serology for Human Immunodeficiency Virus (HIV), or Hepatitis B or C
  • Subjects with other significant disease or disorder that, in the Investigator's opinion, would exclude the subject from the study
  • Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study
  • Unable to swallow tablets

Trial locations and contacts

10 sites in 3 countries.

10 sites in 3 countries

Russia4 sites

  • Study site

    Chelyabinsk

  • Study site

    Krasnodarsky Region

  • Study site

    Saint Petersburg

  • Study site

    Stavropol Krai

Other trials in Russia

Bulgaria3 sites

  • Study site

    Pleven

  • Study site

    Plovdiv

  • Study site

    Sofia

Other trials in Bulgaria

United Kingdom3 sites

  • Study site

    Glasgow

  • Study site

    Leeds

  • Study site

    Newcastle upon Tyne

Other trials in United Kingdom

About this study

Official title: A Phase 1b/2, Multicenter, Open-Label, Dose-Escalation and Confirmation Study of Eribulin in Combination With Capecitabine

This is a Phase 1b/2, multi-center, open-label, dose escalation (in 2 different dosing schedules [1 and 2]) and dose-confirmation study of eribulin administered in combination with capecitabine.

Being tested
Eribulin mesylate, Capecitabine
Keywords
metastatic breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Eribulin mesylateDrug

    Intravenous (IV) bolus or infusion.

  • CapecitabineDrug

    Oral film-coated tablets.

Study groups in NCT01323530
Study groupRoleWhat they receive
Dose-escalation Phase (Phase 1b)ExperimentalParticipants with advanced and/or metastatic tumors will receive eribulin mesylate as a 2 to 5 min Intravenous (IV) bolus or infusion in two different schedules (Schedule 1 [1.2, 1.6, 2.0 mg/m2], given on Day 1 only, and Schedule 2 [0.7, 1.1, 1.7 mg/m^2], given on Days 1 and 8) and oral capecitabine 1000 mg/m2 bid on Days 1-14 (21-day cycles) in both schedules. If maximum tolerated dose (MTD) is not observed at dose level 3 the dose of capecitabine might be escalated to 1250 mg/m^2 bid on Days 1-14 (21-day cycles) depending on the Dose limiting toxicities (DLTs) observed and/or pharmacokinetic (PK) data when available. Based on the data and safety monitoring board review of dose escalation phase data (DLTs that will be observed in first cycle), Dose-Confirmation Phase (Phase 2) will may get initiated.
Receives: Drug: Eribulin mesylate; Drug: Capecitabine
Dose-confirmation Phase (Phase 2)ExperimentalParticipants with advanced and/or metastatic tumors will receive Eribulin mesylate at the MTD for the selected schedule of dose escalation phase based on safety/PK data.
Receives: Drug: Eribulin mesylate; Drug: Capecitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0)

    DLTs as per NCI CTCAE v3.0 were defined as:1) Neutropenia Grade 4 that lasted at least 7 days, 2) Neutropenia Grade 3 or 4 complicated by fever and/or infection (absolute neutrophil count [ANC] less than 1.0*10^9/liter [L], fever of at least 38.5 degree celsius [°C]), 3)Thrombocytopenia Grade 4, 4) Thrombocytopenia Grade 3 complicated by bleeding and/or requiring platelet or blood transfusion, 5) Non-hematological toxicity Grade 3 or higher (excluding Grade 3 nausea, and Grade 3 or 4 vomiting or diarrhea in participants who had not received optimal treatment with antiemetic and/or antidiarrheal medication; excluding laboratory abnormalities without clinical symptoms), 6) Delayed recovery from treatment-related toxicity resulting in dose delay greater than 14 days, 7) Failure to administer at least 75 percent (%) of planned study drugs during Cycle 1 as result of Grade 2 or higher treatment-related toxicity that constituted increase of at least 2 grades from baseline.

    Measured: Cycle 1 (21 days)

  2. Phase 2: Objective Response Rate (ORR)

    ORR was defined as the percentage of participants who had either a confirmed complete response (CR) or partial response (PR). ORR was assessed based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1). CR was defined as disappearance of all target lesions. All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (<) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter. ORR was summarized using the Clopper-Pearson method.

    Measured: From the first dose of study drug until PD or up to 30 days after the last dose of study treatment (up to approximately 3.75 years)

Secondary outcomes (8)

  1. Phase 2: Time to Response

    Time to response (CR or PR) was defined as the time from the first dose until first documented evidence of CR or PR (whichever status was recorded first). Time to response was assessed based on RECIST v 1.1. CR was defined as disappearance of all target lesions. All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter. Time to response was summarized using the Kaplan-Meier method.

    Measured: From the first dose of study drug treatment start date until date of first documented evidence of CR or PR or up to 30 days after the last dose of study treatment (up to approximately 3.75 years)

  2. Phase 2: Duration of Response (DOR)

    DOR: time from first documented evidence of CR or PR until first documented sign of PD or death. DOR was assessed based on RECIST v 1.1. CR: disappearance of all target lesions. All pathological lymph nodes (whether target/non-target) must have a reduction in their short axis to >10 mm. PR: at least a 30% decrease in sum of longest diameter of target lesions, taking as reference the baseline sum of longest diameter. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study). DOR was summarized using the Kaplan-Meier method.

    Measured: From date of the first CR or PR until the date of first documentation of PD or death or up to 30 days after the last dose of study treatment (up to approximately 3.75 years)

  3. Phase 2: Stable Disease (SD) Rate

    SD rate was defined as the percentage of participants with a SD that lasted for a minimum of 5 weeks. SD rate was assessed based on RECIST version 1.1. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PR: at least a 30% decrease in sum of longest diameter of target lesions, taking as reference the baseline sum of longest diameter. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study).

    Measured: From the first dose of study drug until PD or up to 30 days after the last dose of study treatment (up to approximately 3.75 years)

  4. Phase 1b and Phase 2: Percentage of Participants With Non-CR/Non-PD

    Non-CR/Non-PD was for participants who had non-target disease only (minimum duration from randomization to Non-CR/Non-PD >=7 weeks) and assessed by investigator based on RECIST v1.1. Non-CR/Non-PD: persistence of one or more non-target lesions, maintenance of tumor marker level above the normal limits.

    Measured: From the first dose of study drug until PD or up to 30 days after the last dose of study treatment (up to approximately 3.75 years)

  5. Phase 2: Duration of Stable Disease (SD)

    Duration of SD was measured from date of the first dose until progression. Duration of SD was assessed based on RECIST v1.1. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PR: at least a 30% decrease in sum of longest diameter of target lesions, taking as reference the baseline sum of longest diameter. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study). Duration of SD was summarized using the Kaplan-Meier method.

    Measured: From the first dose of study drug until PD or 30 days after the last dose of study treatment (up to approximately 3.75 years)

  6. Phase 2: Disease Control Rate (DCR)

    DCR was defined as the percentage of participants with a confirmed CR, PR, or SD divided by the number of participants in the analysis set. DCR was assessed by an investigator based on RECIST v1.1. CR: disappearance of all target lesions. All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to <10 mm. PR: at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study). DCR was summarized using the Clopper-Pearson method.

    Measured: From the first dose of study drug until PD or 30 days after the last dose of study treatment (up to approximately 3.75 years)

  7. Phase 2: Clinical Benefit Rate (CBR)

    CBR was defined as the percentage of participants with a confirmed CR, PR, or SD of at least 6 months duration (durable SD) divided by the number of participants in the analysis set. CBR was determined by an investigator based on RECIST v1.1. CR: disappearance of all target lesions. All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to <10 mm. PR: at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study). CBR was summarized using the Clopper-Pearson method.

    Measured: From the first dose of study drug until PD or 30 days after the last dose of study treatment (up to approximately 3.75 years)

  8. Phase 2: Progression-free Survival (PFS)

    PFS was defined as the time from the first dose date until PD or death due to any cause. PFS was determined by an investigator based on RECIST v1.1. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study). PFS was summarized using the Kaplan-Meier method.

    Measured: From the first dose of study drug until PD or death due to any cause or 30 days after the last dose of study treatment (up to approximately 3.75 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Mar 2011 (estimated)
  2. Study start26 Jan 2010
  3. Primary completion28 Jul 2014
  4. Study completion13 Oct 2015

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
76 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01323530
Sponsor's protocol ID
E7389-E044-203
Other IDs
2009-011217-24, 2009
Status last verified
Aug 2020
First submitted
24 Mar 2011
Last updated
11 Jan 2021
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Twelves C, Anthoney A, Savulsky CI, Guo M, Reyderman L, Cresti N, Semiglazov V, Timcheva C, Zubairi I, Morrison R, Plummer R, Evans TRJ. A phase 1b/2, open-label, dose-escalation, and dose-confirmation study of eribulin mesilate in combination with capecitabine. Br J Cancer. 2019 Mar;120(6):579-586. doi: 10.1038/s41416-018-0366-5. Epub 2019 Feb 20.

    PubMed 30783204

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Eribulin mesylate and Capecitabine in people with Metastatic Breast Cancer, run by Eisai Limited at 10 sites in 3 countries.

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 29 inclusion and 19 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: finished, as of the sponsor's last update on 11 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Russia, Bulgaria, United Kingdom. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Yes. Results are posted in the registry (first posted 11 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) (time frame: Cycle 1 (21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01323530, which also lists 1 linked publication.

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 11 Jan 2021.

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