A Confirmation Study of Eribulin in Combination With Capecitabine
- Conditions
- Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT01323530
- Lead Sponsor
- Eisai Limited
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 76
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose-escalation Phase (Phase 1b) Capecitabine 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. Dose-confirmation Phase (Phase 2) Eribulin mesylate 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. Dose-escalation Phase (Phase 1b) Eribulin mesylate 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. Dose-confirmation Phase (Phase 2) Capecitabine 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.
- Primary Outcome Measures
Name Time Method 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) Cycle 1 (21 days) 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.
Phase 2: Objective Response Rate (ORR) 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) 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.
- Secondary Outcome Measures
Name Time Method Phase 2: Duration of Stable Disease (SD) 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) 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.
Phase 2: Progression-free Survival (PFS) 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) 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.
Phase 1b and Phase 2: Percentage of Participants With Non-CR/Non-PD 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) 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.
Phase 2: Time to Response 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) 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.
Phase 2: Stable Disease (SD) Rate 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) 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).
Phase 2: Duration of Response (DOR) 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) 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.
Phase 2: Disease Control Rate (DCR) 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) 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.
Phase 2: Clinical Benefit Rate (CBR) 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) 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.