Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Antimetabolites

Participants 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.

Participants 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.

Eribulin mesylate

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.

A Confirmation Study of Eribulin in Combination With Capecitabine

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

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

Eisai Limited

The safety set included the group of participants who received study drug and had at least 1 post dose safety assessment.

Participants received eribulin mesilate 1.2 mg/m\^2, injection, intravenously, once, on Day 1 and capecitabine 1000 mg/m\^2, tablets, orally, twice daily from Day 1 to 14 in each 21-day treatment cycle for as long as the treatment was clinically appropriate according to the judgment of the investigator or until the occurrence of PD, undue toxicity, the presence of other medical conditions that prohibit continuation of therapy, pregnancy, a delay of more than 14 days in starting the next cycle during Phase 1b (Schedule 1).

Phase 1b (Schedule 1): Eribulin Mesilate (1.2 mg/m^2)

Participants received eribulin mesilate 1.6 mg/m\^2, injection, intravenously, once, on Day 1 and capecitabine 1000 mg/m\^2, tablets, orally, twice daily from Day 1 to 14 in each 21-day treatment cycle for as long as the treatment was clinically appropriate according to the judgment of the investigator or until the occurrence of PD, undue toxicity, the presence of other medical conditions that prohibit continuation of therapy, pregnancy, a delay of more than 14 days in starting the next cycle during Phase 1b (Schedule 1).

Phase 1b (Schedule 1): Eribulin Mesilate (1.6 mg/m^2)

Participants received eribulin mesilate 2.0 mg/m\^2, injection, intravenously, once, on Day 1 and capecitabine 1000 mg/m\^2, tablets, orally, twice daily from Day 1 to 14 in each 21-day treatment cycle for as long as the treatment was clinically appropriate according to the judgment of the investigator or until the occurrence of PD, undue toxicity, the presence of other medical conditions that prohibit continuation of therapy, pregnancy, a delay of more than 14 days in starting the next cycle during Phase 1b (Schedule 1).

Phase 1b (Schedule 1): Eribulin Mesilate (2.0 mg/m^2)

Participants received eribulin mesilate 0.7 mg/m\^2, injection, intravenously, once, on Days 1 and 8, and capecitabine 1000 mg/m\^2, tablets, orally, twice daily from Day 1 to 14 in each 21-day treatment cycle for as long as the treatment was clinically appropriate according to the judgment of the investigator or until the occurrence of PD, undue toxicity, the presence of other medical conditions that prohibit continuation of therapy, pregnancy, a delay of more than 14 days in starting the next cycle during Phase 1b (Schedule 2).

Phase 1b (Schedule 2): Eribulin Mesilate (0.7 mg/m^2)

Participants received eribulin mesilate 1.1 mg/m\^2, injection, intravenously, once, on Days 1 and 8, and capecitabine 1000 mg/m\^2, tablets, orally, twice daily from Day 1 to 14 in each 21-day treatment cycle for as long as the treatment was clinically appropriate according to the judgment of the investigator or until the occurrence of PD, undue toxicity, the presence of other medical conditions that prohibit continuation of therapy, pregnancy, a delay of more than 14 days in starting the next cycle during Phase 1b (Schedule 2).

Phase 1b (Schedule 2): Eribulin Mesilate (1.1 mg/m^2)

Participants received eribulin mesilate 1.4 mg/m\^2, injection, intravenously, once, on Days 1 and 8, and capecitabine 1000 mg/m\^2, tablets, orally, twice daily from Day 1 to 14 in each 21-day treatment cycle for as long as the treatment was clinically appropriate according to the judgment of the investigator or until the occurrence of PD, undue toxicity, the presence of other medical conditions that prohibit continuation of therapy, pregnancy, a delay of more than 14 days in starting the next cycle during Phase 1b (Schedule 2).

Phase 1b (Schedule 2): Eribulin Mesilate (1.4 mg/m^2)

Participants received eribulin mesilate 1.4 mg/m\^2, injection, intravenously, once, on Days 1 and 8, and capecitabine 1000 mg/m\^2, tablets, orally, twice daily from Day 1 to 14 in each 21-day treatment cycle for as long as the treatment was clinically appropriate according to the judgment of the investigator or until the occurrence of PD, undue toxicity, the presence of other medical conditions that prohibit continuation of therapy, pregnancy, a delay of more than 14 days in starting the next cycle during Phase 2.

Phase 2: Eribulin Mesilate 1.4 mg/m^2

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Full Analysis Set included all participants who were enrolled and received at least 1 dose of study drug.

Eisai Medical Information

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)

The Dose-confirmation full analysis set included all participants who enrolled in the Dose-confirmation Cohort (Phase 2) and received at least 1 dose of drug.

Phase 2: Objective Response Rate (ORR)

The Dose-confirmation full analysis set included all participants who enrolled in the Dose-confirmation Cohort (Phase 2) and received at least 1 dose of drug. Here "overall number of participants analyzed" signifies participants who had CR or PR.

Phase 2: Time to Response

Phase 2: Duration of Response (DOR)

Phase 2: Stable Disease (SD) Rate

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

The Dose-confirmation full analysis set included all participants who enrolled in the Dose-confirmation Cohort (Phase 2) and received at least 1 dose of drug. Here "overall number of participants analyzed" signifies participants who had SD.

Phase 2: Duration of Stable Disease (SD)

Phase 2: Disease Control Rate (DCR)

Phase 2: Clinical Benefit Rate (CBR)

Phase 2: Progression-free Survival (PFS)

Participants received eribulin mesilate 1.2 milligrams per square meter (mg/m\^2), injection, intravenously, once, on Day 1 and capecitabine 1000 mg/m\^2, tablets, orally, twice daily from Day 1 to 14 in each 21-day treatment cycle for as long as the treatment was clinically appropriate according to the judgment of the investigator or until the occurrence of progressive disease (PD), undue toxicity, the presence of other medical conditions that prohibit continuation of therapy, pregnancy, a delay of more than 14 days in starting the next cycle during Phase 1b (Schedule 1).

Spots Global Cancer Trial Database for A Confirmation Study of Eribulin in Combination With Capecitabine

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Study Description

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