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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-001184-69 | EudraCT Number |
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Study E7389-E044-112 is a Phase 1 study designed to assess the safety, tolerability and preliminary efficacy of eribulin-liposomal formulation (E7389-LF) in patients with solid tumors. This dose-escalation study will determine the maximum tolerated dose, dosing schedules tested, the dose schedule regimen with a more favorable tolerability profile, and a preliminary indication of efficacy.
This is a Phase 1 first-in-human, non-randomized (individuals will not be assigned by chance to study treatments), open-label (individuals will know the identity of study treatments), multicenter, 2-part, dose-escalation study to evaluate the safety, pharmacokinetics (study of what the body does to a drug) of eribulin-LF administered intravenously to patients with solid tumors. Each treatment cycle will be 21 days (Schedule 1) or 28 days (Schedule 1a or 2). Part 1 is the dose-escalation phase, which will be guided by pharmacokinetics and safety. Three to 6 new patients will be enrolled in sequential cohorts (first cohort will receive the starting dose and subsequent cohorts will receive increased doses of eribulin-LF). Enrollment in each cohort will be staggered; the second and third participant in every cohort will not be dosed until the first patient in that cohort completes 2 weeks of Cycle 1. If no dose-limiting toxicities (DLTs) have been observed during the first 2 week of Cycle 1 in the first patient, the second and third patients in the cohort will initiate treatment. Enrollment will be first initiated into cohort 1 of Schedule 1 (dosing on Day 1 of 21 day cycle). Interim analysis will be conducted upon completion of this cohort. The following decisions will be made based upon the results of the interim analysis 1) proceed with escalating to next dose level (cohort 2) of Schedule 1 (dosing on Day 1 of 21 day cycle) and initiate cohort 1 of Schedule 2 (dosing on Day 1 and Day 15 of 28 day cycle), or 2) discontinue plans to evaluate Schedule 2 and initiate Schedule 1a (dosing on Day 1 of 28 day cycle).
After the last patient in each cohort completes Cycle 1, the safety for DLT determination will be evaluated and a decision will be made on whether to escalate the dose in a new cohort of 3 to 6 new patients. Dose escalation will halt when the maximum tolerated dose (MTD) is reached. The total number of patients to be enrolled in Part 1 will depend on the dose level at which the DLT will be achieved. After MTD for each schedule is determined, patients will be enrolled into Expansion Part of the study to confirm safety and tolerability of each dosing schedule. Nine to 12 patients will be treated with MTD for each schedule for 6 cycles. The total study duration for each participant will be approximately 18 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Eribulin-LF Schedule 1 | Experimental | Schedule 1: Eribulin-LF administered as IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating up to 3.5 mg/m^2. Schedule 1a: Eribulin-LF administered as IV infusion on Day 1 of a 28-day cycle starting at 1 mg/m^2 escalating up to 3.5 mg/m^2 (only to be investigated in the event that a 21-day cycle is considered inappropriate). |
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| Eribulin-LF Schedule 2 | Experimental | Schedule 2: Eribulin-LF administered as IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating up to 3.5 mg/m^2 (only to be investigated in the event that a 21-day cycle is considered appropriate). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Eribulin-LF | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Eribulin-LF | The MTD was defined as the highest dose level at which no more than 1/6 participants experienced a dose limiting toxicity (DLTs), with the next higher dose having at least 2 of 3 or 2 of 6 participants experiencing DLTs. MTD was determined by summarizing the number and percentage of participants with DLTs for the first cycle, by study dosing schedule, initial dosing level and overall for the dose escalation part. For participants who continued to Cycle 2, the DLTs which occurred from 1st dose up to the day before Day 1 of Cycle 2 were counted. For participants who discontinued before Cycle 2, the DLTs which occurred from 1st dose up to Day 21 (Schedule 1) or Day 28 (Schedule 2) of Cycle 1 were counted. DLTs were evaluated and graded based on the National Cancer Institutes (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | Schedule 1: Cycle 1 (21 days); Schedule 2: Cycle 1 (28 days) |
| Dose Limiting Toxicities at the Indicated Dose Levels, as an Assessment of Dosing Frequency | DLTs were evaluated for both Schedule 1 and Schedule 2. DLTs were defined as neutropenia grade 4 that lasted more than 5 days, neutropenia grade 3 or 4 complicated by fever and/or infection (absolute neutrophil count (ANC) less than 1.0 x 10^9/liter, fever greater than or equal to 38.5 degrees Celsius), thrombocytopenia grade 4 of any duration, thrombocytopenia grade 3 complicated by bleeding and/or requiring platelet or blood transfusion, hypersensitivity reaction grade 3 or 4 including allergy reactions or anaphylaxis; symptomatic bronchospasm requiring parenteral medication(s) with our without urticarial; allergy-related edema/angioedema, or other grade 3 or 4 clinically significant non-hematologic toxicities (except for inadequately treated nausea and /or vomiting) considered related to study drug. Participants with two or more adverse events in the same system organ class (or with the same preferred term) was counted only once for that system organ class (or preferred term). | Cycle 1 of Dose Escalation part in Schedule 1 and Schedule 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability of Eribulin-LF | Safety was assessed by the monitoring and recording of all adverse events (AEs), and serious AEs (SAEs), regular monitoring of hematology, clinical chemistry, and urine values; periodic measurement of vital signs, electrocardiograms; and the performance of physical examinations. For each row category, a participant with two or more adverse events in that category is counted only once. Treatment-related TEAEs include TEAEs that were considered by the Investigator to be possibly or probably related to study drug and TEAEs with a missing relationship to study drug. |
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Inclusion Criteria:
Exclusion Criteria:
Females who are pregnant (positive B-hCG [or hCG] test) or breastfeeding.
Participants who have received any anticancer therapy within 21 days prior to study entry for cytotoxic agents (42 days for mitomycin C and nitrosoureas), radiotherapy, hormonal, biological (including humanized antibodies) and targeted agents, or within 30 days for an investigational agent.
Participants who have not recovered from acute toxicities as a result of prior anti-cancer therapy to less than Grade 2, according to Common Terminology Criteria for Adverse Events (CTCAE), except alopecia.
Participants who have previously been treated with eribulin-LF.
Radiation therapy encompassing greater than 30% of the bone marrow.
Major surgery within 21 days prior to enrollment.
Pre-existing peripheral neuropathy greater than CTCAE Grade 1.
Significant cardiovascular impairment, defined as:
Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments.
Diagnosed with meningeal carcinomatosis.
Participants with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks prior to enrollment. Any symptom(s) attributed to brain metastases must be stable for at least 4 weeks prior to enrollment, and radiographic stability should be confirmed by comparing a brain scan (CT with contrast or MRI with and without contrast) performed during the Screening Period to a brain scan performed at least 4 weeks earlier using the same modality.
Any serious concomitant illness or infection requiring treatment: known active human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C infection (asymptomatic positive serology is not exclusionary).
Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
History of drug or alcohol dependency or abuse within approximately the last 2 years or current use of illegal recreational drugs.
Known intolerance to Halaven (eribulin-LF; E7389-LF) or any of the excipients.
Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study.
Scheduled for surgery during the study.
Participants with body mass index (BMI) less than 35.
Participants with proven abdominal malignancy with concurrent refractory ascites defined by one of the following criteria:
Participants with concurrent refractory pleural effusion defined by the following criteria:
Currently enrolled in another clinical trial or used any investigational drug or device within 30 days or 5X the half-life, whichever is longer preceding informed consent.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Marsden Hospital | Sutton | Surrey | United Kingdom | |||
| Beatson West of Scotland Cancer Centre |
Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.
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Total 71 subjects were screened for entry into the study of which 62 were enrolled and 9 were screen failures. Of the 9 screen failures, 7 did not meet the inclusion/exclusion criteria, 1 experienced an adverse event that led to screening discontinuation, and 1 did not proceed to treatment in the study. Of the 62 enrolled, 58 subjects were treated.
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| ID | Title | Description |
|---|---|---|
| FG000 | Schedule 1 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 milligram per square meter [mg/m^2]) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| From date of first dose until 30 days after the final dose of study drug, up to approximately 3 years 6 months |
| Maximum Plasma Concentration (Cmax) of Eribulin-LF | Blood samples for Schedule 1 were drawn on Cycle 1/Day 1 and Cycle 3/Day 1 predose, 15 minutes (min) after the start of infusion (SOI), 5 min after the end of infusion (EOI), 0.5, 1, 2, 4, 6, 8, and 24 hours (h) postdose, and Day 4, Day 7, Day 9, and Day 11. Blood samples for Schedule 2 were drawn on Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9 and Day 11. Some participants followed a different pharmacokinetic (PK) assessment schedule prior to protocol amendment 3. Plasma concentrations of eribulin-LF were determined using a validated liquid chromatography-tandem mass spectrometry (LC/MS/MS) method. Plasma PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of Cmax, which was then summarized as the mean and standard deviation for all participants and expressed as nanograms/milliliter (ng/mL). | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
| Time to Maximum Plasma Concentration (Tmax) of Eribulin-LF | Blood samples for Schedule 1 were drawn on Cycle 1/Day 1 and Cycle 3/Day 1 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9, and Day 11. Blood samples for Schedule 2 were drawn on Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9 and Day 11. Some participants followed a different PK assessment schedule prior to protocol amendment 3. Plasma concentrations of eribulin-LF were determined using a validated LC/MS/MS method. Plasma PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of Tmax, which was then summarized as the median and full range for all participants and expressed as hours. | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
| Plasma Half-life (t1/2) of Eribulin-LF | Blood samples for Schedule 1 were drawn on Cycle 1/Day 1 and Cycle 3/Day 1 predose, 15 min after SOI, 5 min after EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9, and Day 11. Blood samples for Schedule 2 were drawn on Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9 and Day 11. Plasma concentrations of eribulin-LF were determined using a validated LC/MS/MS method. Plasma PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of t1/2, which was then summarized as the mean and standard deviation for all participants and expressed in hours. | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
| Area Under the Plasma Concentration-Time Curve From Time 0 Time of Last Quantifiable Concentration (AUC(0-t) ) of Eribulin-LF | Blood samples for Schedule 1 were drawn on Cycle 1/Day 1 and Cycle 3/Day 1 predose, 15 min after SOI, 5 min after EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9, and Day 11. Blood samples for Schedule 2 were drawn on Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9 and Day 11. Plasma concentrations of eribulin-LF were determined using a validated LC/MS/MS method. Plasma PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of AUC(0-t), which was then summarized as the mean and standard deviation for all participants and expressed in nanograms*hour/milliliter (ng*hr/mL). | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
| Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf)) of Eribulin-LF | Blood samples for Schedule 1 were drawn on Cycle 1/Day 1 and Cycle 3/Day 1 predose, 15 min after SOI, 5 min after EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9, and Day 11. Blood samples for Schedule 2 were drawn on Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9 and Day 11. Plasma concentrations of eribulin-LF were determined using a validated LC/MS/MS method. Plasma PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of AUC(0-inf), which was then summarized as the mean and standard deviation for all participants and expressed in ng*hr/mL. | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
| Total Body Clearance (CL) of Eribulin-LF | Blood samples for Schedule 1 were drawn on Cycle 1/Day 1 and Cycle 3/Day 1 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9, and Day 11. Blood samples for Schedule 2 were drawn on Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9 and Day 11. Some participants followed a different PK assessment schedule prior to protocol amendment 3. Plasma concentrations of eribulin-LF were determined using a validated LC/MS/MS method. Plasma PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of CL, which was then summarized as the mean and standard deviation for all participants and expressed as milliliter/hour (mL/h). | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
| Volume of Distribution (Vd) of Eribulin-LF | Blood samples for Schedule 1 were drawn on Cycle 1/Day 1 and Cycle 3/Day 1 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9, and Day 11. Blood samples for Schedule 2 were drawn on Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9 and Day 11. Some participants followed a different PK assessment schedule prior to protocol amendment 3. Plasma concentrations of eribulin-LF were determined using a validated LC/MS/MS method. Plasma PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of Vd, which was then summarized as the mean and standard deviation for all participants and expressed as milliliters (mL). | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
| Renal Clearance (CLr) of Eribulin-LF | Blood samples for Schedule 1 were drawn on Cycle 1/Day 1 and Cycle 3/Day 1 predose, 15 min after SOI, 5 min after EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9, and Day 11. Blood samples for Schedule 2 were drawn on Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 predose, 15 min after SOI, 5 min after EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9 and Day 11. Some participants followed a different PK assessment schedule prior to protocol amendment 3. Plasma concentrations of eribulin-LF were determined using a validated LC/MS/MS method. Plasma PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of CLr, which was then summarized as the mean and standard deviation for all participants and expressed in liters/hour (L/hr). | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
| Fraction of Unchanged Eribulin-LF Excreted in the Urine (fe) | Urinalysis was performed at Screening, Baseline, Cycle 1/Day 15, and each study visit of every cycle thereafter. If urinalysis suggested a urinary tract infection, or if clinically indicated, a urine microscopy, culture, and sensitivity was to be performed at the institution's laboratory. If urine protein was ≥ 2+ on urinalysis, then a 24-hour urine collection was to be done to quantify the 24-hour urine protein excretion. The samples were analyzed for the amount of eribulin in the urine using liquid LC/MS method of analysis. Urine PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of fe, which was then summarized as the mean and standard deviation for all participants and expressed in percentage of eribulin-LF. | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
| Percentage of Participants With Best Overall Response (BOR) | BOR to treatment was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. BOR was the best confirmed response of complete response (CR), partial response (PR), progressive disease (PD), stable disease (SD), or not evaluable (NE), recorded from the start of eribulin-LF until disease progression/recurrence or death. CR; disappearance of all target lesions for at least 1 month. PR; at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD; at least 20% or greater increase in the sum of the longest diameter of measured lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of one or more new lesions. SD; PR failed to be achieved in the overall response assessment and there was no PD observed at the end of 6 cycles or later after starting eribulin-LF. | Baseline to first date of documented CR, PR, SD, or PD, assessed up to data cutoff date (17 May 2016), for up to approximately 3 years 7 months |
| Percentage of Participants With Objective Response Rate (ORR) | ORR was defined as the percentage of participants with BOR of CR or PR based on RECIST v1.1 criteria or target lesions assessed by magnetic resonance imaging/computed tomography (MRI/CT) scans, as determined by independent radiologic review. BOR of CR was confirmed by a subsequent CR assessment at least 4 weeks later. BOR of PR was confirmed by a subsequent CR or PR assessment at least 4 weeks later. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than 10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters. The null hypothesis ORR was less than or equal to 10% was tested using 1-sided exact test of a single proportion, at 1-sided 0.05 level. ORR was presented with corresponding 2-sided, 95% confidence interval (CI). ORR=CR+PR. | From date of treatment start until disease progression, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment, or up to data cutoff date (17 May 2016), for up to approximately 3 years 7 months |
| Percentage of Participants With Disease Control Rate (DCR) | DCR was the percentage of the participants who had BOR of CR, PR, and SD, based on assessments by each site investigator using RECIST v1.1. The minimum duration of SD was defined as 5 weeks (or 7 weeks for Schedules 1a and 2 in the Dose Escalation Part) following the date of the first dose of study drug in order for stable disease to be considered the best overall response. The 95% CI was constructed using the method of Clopper and Pearson. DCR = CR + PR + SD | From date of treatment start until disease progression, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment, or up to data cutoff date (17 May 2016), for up to approximately 3 years 7 months |
| Percentage of Participants With Clinical Benefit Rate (CBR) | CBR was defined as the percentage of participants with BOR of CR or PR or durable stable disease (dSD) [CR + PR + dSD] based on RECIST v1.1. The dSD rate was defined as the percentage of participants with dSD (based on RECIST 1.1 and defined as SD lasting greater than or equal to 6 months), as determined by the site Investigator. | From date of treatment start until disease progression, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment, or up to data cutoff date (17 May 2016), for up to approximately 3 years 7 months |
| Percentage of Participants With Progression Free Survival (PFS) | PFS was defined as the time from the date of treatment start until progressive disease or death from any cause in the absence of progressive disease. Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions (taking as reference the smallest sum on study), recorded since the treatment started or the appearance of 1 or more new lesions as assessed by IRR using RECIST v1.1. The duration of PFS was calculated as end date minus date of first drug plus 1, based on assessments by the site Investigator. PFS was calculated using Kaplan-Meier estimate and presented with 2-sided 95% Cl. | From date of treatment start until disease progression, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment, or up to data cutoff date (17 May 2016), for up to approximately 3 years 7 months |
| Number of Participants With the Indicated Shift From Baseline Category to the Indicated Worst Post-Baseline Category | The effects of eribulin-LF on cardiovascular repolarization were evaluated via 24-hour, 12-lead continuous Holter electrocardiogram (ECG) monitoring in Cycle 1, Day 1 for Schedule 1 and Day 1 and Day 15 of Schedule 2. Individual ECGs were extracted in triplicate from the Holter recordings at specified time points and were evaluated by a central laboratory. QT intervals were measured from Lead II and were corrected for heart rate (QTc) using Fridericia's (QTcF) and Bazett's (QTcB) correction factors. The primary QTc parameter was QTcF. Secondary parameters (QTcB, QT, QRS, and hazard ratio/heart rate (HR)) and waveforms (T-waves) were evaluated. BL= Baseline, PBL = post-Baseline, A,NCS = abnormal, not clinically significant, A, CS = abnormal, clinically significant | Baseline (Day -1), Schedule 1 (Cycle 1 Day 1); Schedule 2 (Cycle 1 Day 1 and Day 15) |
| Glasgow |
| United Kingdom |
| UCL Cancer Institute | London | United Kingdom |
| The Christie NHS Foundation Trust | Manchester | United Kingdom |
| Schedule 1 Dose Escalation Cohort: 1.4 mg/m^2 Eribulin-LF |
Dose Escalation Cohort: Eribulin-LF (1.4 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| FG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| FG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| FG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| FG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| FG006 | Schedule 2 Expansion Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Expansion Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle. |
| COMPLETED |
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| NOT COMPLETED |
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The Safety Analysis Set (SAS) was the group of participants who received study drug and had at least 1 post-dose safety assessment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Schedule 1 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| BG001 | Schedule 1 Dose Escalation Cohort: 1.4 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.4 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| BG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| BG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| BG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| BG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| BG006 | Schedule 2 Expansion Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Expansion Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle. |
| BG007 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
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| Primary | Maximum Tolerated Dose (MTD) of Eribulin-LF | The MTD was defined as the highest dose level at which no more than 1/6 participants experienced a dose limiting toxicity (DLTs), with the next higher dose having at least 2 of 3 or 2 of 6 participants experiencing DLTs. MTD was determined by summarizing the number and percentage of participants with DLTs for the first cycle, by study dosing schedule, initial dosing level and overall for the dose escalation part. For participants who continued to Cycle 2, the DLTs which occurred from 1st dose up to the day before Day 1 of Cycle 2 were counted. For participants who discontinued before Cycle 2, the DLTs which occurred from 1st dose up to Day 21 (Schedule 1) or Day 28 (Schedule 2) of Cycle 1 were counted. DLTs were evaluated and graded based on the National Cancer Institutes (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | Dose finding analysis set is all participants in the dose escalation part who completed Cycle 1 treatment and were evaluated for DLTs, and those who discontinued during Cycle 1 due to DLT. | Posted | Number | mg/m^2 | Schedule 1: Cycle 1 (21 days); Schedule 2: Cycle 1 (28 days) |
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| Primary | Dose Limiting Toxicities at the Indicated Dose Levels, as an Assessment of Dosing Frequency | DLTs were evaluated for both Schedule 1 and Schedule 2. DLTs were defined as neutropenia grade 4 that lasted more than 5 days, neutropenia grade 3 or 4 complicated by fever and/or infection (absolute neutrophil count (ANC) less than 1.0 x 10^9/liter, fever greater than or equal to 38.5 degrees Celsius), thrombocytopenia grade 4 of any duration, thrombocytopenia grade 3 complicated by bleeding and/or requiring platelet or blood transfusion, hypersensitivity reaction grade 3 or 4 including allergy reactions or anaphylaxis; symptomatic bronchospasm requiring parenteral medication(s) with our without urticarial; allergy-related edema/angioedema, or other grade 3 or 4 clinically significant non-hematologic toxicities (except for inadequately treated nausea and /or vomiting) considered related to study drug. Participants with two or more adverse events in the same system organ class (or with the same preferred term) was counted only once for that system organ class (or preferred term). | Dose-finding analysis set included all participants in the dose escalation part who completed Cycle 1 treatment and were evaluated for DLTs and those who discontinued during Cycle 1 due to DLTs. | Posted | Count of Participants | Participants | Cycle 1 of Dose Escalation part in Schedule 1 and Schedule 2 |
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| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability of Eribulin-LF | Safety was assessed by the monitoring and recording of all adverse events (AEs), and serious AEs (SAEs), regular monitoring of hematology, clinical chemistry, and urine values; periodic measurement of vital signs, electrocardiograms; and the performance of physical examinations. For each row category, a participant with two or more adverse events in that category is counted only once. Treatment-related TEAEs include TEAEs that were considered by the Investigator to be possibly or probably related to study drug and TEAEs with a missing relationship to study drug. | The SAS was the group of participants who received study drug and had at least 1 post-dose safety assessment. | Posted | Count of Participants | Participants | From date of first dose until 30 days after the final dose of study drug, up to approximately 3 years 6 months |
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| Secondary | Maximum Plasma Concentration (Cmax) of Eribulin-LF | Blood samples for Schedule 1 were drawn on Cycle 1/Day 1 and Cycle 3/Day 1 predose, 15 minutes (min) after the start of infusion (SOI), 5 min after the end of infusion (EOI), 0.5, 1, 2, 4, 6, 8, and 24 hours (h) postdose, and Day 4, Day 7, Day 9, and Day 11. Blood samples for Schedule 2 were drawn on Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9 and Day 11. Some participants followed a different pharmacokinetic (PK) assessment schedule prior to protocol amendment 3. Plasma concentrations of eribulin-LF were determined using a validated liquid chromatography-tandem mass spectrometry (LC/MS/MS) method. Plasma PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of Cmax, which was then summarized as the mean and standard deviation for all participants and expressed as nanograms/milliliter (ng/mL). | The PK analysis set was the group of participants who had sufficient PK data to derive at least one PK parameter. | Posted | Mean | Standard Deviation | ng/mL | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
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| Secondary | Time to Maximum Plasma Concentration (Tmax) of Eribulin-LF | Blood samples for Schedule 1 were drawn on Cycle 1/Day 1 and Cycle 3/Day 1 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9, and Day 11. Blood samples for Schedule 2 were drawn on Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9 and Day 11. Some participants followed a different PK assessment schedule prior to protocol amendment 3. Plasma concentrations of eribulin-LF were determined using a validated LC/MS/MS method. Plasma PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of Tmax, which was then summarized as the median and full range for all participants and expressed as hours. | The PK analysis set was the group of participants who had sufficient PK data to derive at least one PK parameter. | Posted | Median | Full Range | hours | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
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| Secondary | Plasma Half-life (t1/2) of Eribulin-LF | Blood samples for Schedule 1 were drawn on Cycle 1/Day 1 and Cycle 3/Day 1 predose, 15 min after SOI, 5 min after EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9, and Day 11. Blood samples for Schedule 2 were drawn on Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9 and Day 11. Plasma concentrations of eribulin-LF were determined using a validated LC/MS/MS method. Plasma PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of t1/2, which was then summarized as the mean and standard deviation for all participants and expressed in hours. | The PK analysis set was the group of participants who had sufficient PK data to derive at least one PK parameter. | Posted | Mean | Standard Deviation | hours | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
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| Secondary | Area Under the Plasma Concentration-Time Curve From Time 0 Time of Last Quantifiable Concentration (AUC(0-t) ) of Eribulin-LF | Blood samples for Schedule 1 were drawn on Cycle 1/Day 1 and Cycle 3/Day 1 predose, 15 min after SOI, 5 min after EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9, and Day 11. Blood samples for Schedule 2 were drawn on Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9 and Day 11. Plasma concentrations of eribulin-LF were determined using a validated LC/MS/MS method. Plasma PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of AUC(0-t), which was then summarized as the mean and standard deviation for all participants and expressed in nanograms*hour/milliliter (ng*hr/mL). | The PK analysis set was the group of participants who had sufficient PK data to derive at least one PK parameter. | Posted | Mean | Standard Deviation | ng*h/mL | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
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| Secondary | Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf)) of Eribulin-LF | Blood samples for Schedule 1 were drawn on Cycle 1/Day 1 and Cycle 3/Day 1 predose, 15 min after SOI, 5 min after EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9, and Day 11. Blood samples for Schedule 2 were drawn on Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9 and Day 11. Plasma concentrations of eribulin-LF were determined using a validated LC/MS/MS method. Plasma PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of AUC(0-inf), which was then summarized as the mean and standard deviation for all participants and expressed in ng*hr/mL. | The PK analysis set was the group of participants who had sufficient PK data to derive at least one PK parameter. | Posted | Mean | Standard Deviation | ng*h/mL | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
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| Secondary | Total Body Clearance (CL) of Eribulin-LF | Blood samples for Schedule 1 were drawn on Cycle 1/Day 1 and Cycle 3/Day 1 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9, and Day 11. Blood samples for Schedule 2 were drawn on Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9 and Day 11. Some participants followed a different PK assessment schedule prior to protocol amendment 3. Plasma concentrations of eribulin-LF were determined using a validated LC/MS/MS method. Plasma PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of CL, which was then summarized as the mean and standard deviation for all participants and expressed as milliliter/hour (mL/h). | The PK analysis set was the group of participants who had sufficient PK data to derive at least one PK parameter. | Posted | Mean | Standard Deviation | mL/h | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
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| Secondary | Volume of Distribution (Vd) of Eribulin-LF | Blood samples for Schedule 1 were drawn on Cycle 1/Day 1 and Cycle 3/Day 1 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9, and Day 11. Blood samples for Schedule 2 were drawn on Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 predose, 15 min after the SOI, 5 min after the EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9 and Day 11. Some participants followed a different PK assessment schedule prior to protocol amendment 3. Plasma concentrations of eribulin-LF were determined using a validated LC/MS/MS method. Plasma PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of Vd, which was then summarized as the mean and standard deviation for all participants and expressed as milliliters (mL). | The PK analysis set was the group of participants who had sufficient PK data to derive at least one PK parameter. | Posted | Mean | Standard Deviation | mL | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
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| Secondary | Renal Clearance (CLr) of Eribulin-LF | Blood samples for Schedule 1 were drawn on Cycle 1/Day 1 and Cycle 3/Day 1 predose, 15 min after SOI, 5 min after EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9, and Day 11. Blood samples for Schedule 2 were drawn on Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 predose, 15 min after SOI, 5 min after EOI, 0.5, 1, 2, 4, 6, 8, and 24 h postdose, and Day 4, Day 7, Day 9 and Day 11. Some participants followed a different PK assessment schedule prior to protocol amendment 3. Plasma concentrations of eribulin-LF were determined using a validated LC/MS/MS method. Plasma PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of CLr, which was then summarized as the mean and standard deviation for all participants and expressed in liters/hour (L/hr). | The PK analysis set was the group of participants who had sufficient PK data to derive at least one PK parameter. | Posted | Mean | Standard Deviation | mL/h | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
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| Secondary | Fraction of Unchanged Eribulin-LF Excreted in the Urine (fe) | Urinalysis was performed at Screening, Baseline, Cycle 1/Day 15, and each study visit of every cycle thereafter. If urinalysis suggested a urinary tract infection, or if clinically indicated, a urine microscopy, culture, and sensitivity was to be performed at the institution's laboratory. If urine protein was ≥ 2+ on urinalysis, then a 24-hour urine collection was to be done to quantify the 24-hour urine protein excretion. The samples were analyzed for the amount of eribulin in the urine using liquid LC/MS method of analysis. Urine PK data were analyzed using a noncompartmental analysis approach to obtain individual participant estimates of fe, which was then summarized as the mean and standard deviation for all participants and expressed in percentage of eribulin-LF. | The PK analysis set was the group of participants who had sufficient PK data to derive at least one PK parameter. | Posted | Mean | Standard Deviation | percent of eribulin-LF | Schedule 1: Cycle 1/Day 1 and Cycle 3/Day 1; Schedule 2: Cycle 1/Day 1 and Day 15 and Cycle 3/Day 1 and Day 15 |
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| Secondary | Percentage of Participants With Best Overall Response (BOR) | BOR to treatment was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. BOR was the best confirmed response of complete response (CR), partial response (PR), progressive disease (PD), stable disease (SD), or not evaluable (NE), recorded from the start of eribulin-LF until disease progression/recurrence or death. CR; disappearance of all target lesions for at least 1 month. PR; at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD; at least 20% or greater increase in the sum of the longest diameter of measured lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of one or more new lesions. SD; PR failed to be achieved in the overall response assessment and there was no PD observed at the end of 6 cycles or later after starting eribulin-LF. | The SAS was the group of participants who received study drug and had at least 1 post-dose safety assessment. | Posted | Number | percentage of participants | Baseline to first date of documented CR, PR, SD, or PD, assessed up to data cutoff date (17 May 2016), for up to approximately 3 years 7 months |
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| Secondary | Percentage of Participants With Objective Response Rate (ORR) | ORR was defined as the percentage of participants with BOR of CR or PR based on RECIST v1.1 criteria or target lesions assessed by magnetic resonance imaging/computed tomography (MRI/CT) scans, as determined by independent radiologic review. BOR of CR was confirmed by a subsequent CR assessment at least 4 weeks later. BOR of PR was confirmed by a subsequent CR or PR assessment at least 4 weeks later. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than 10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters. The null hypothesis ORR was less than or equal to 10% was tested using 1-sided exact test of a single proportion, at 1-sided 0.05 level. ORR was presented with corresponding 2-sided, 95% confidence interval (CI). ORR=CR+PR. | The SAS was the group of participants who received study drug and had at least 1 post-dose safety assessment. | Posted | Median | 95% Confidence Interval | percentage of participants | From date of treatment start until disease progression, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment, or up to data cutoff date (17 May 2016), for up to approximately 3 years 7 months |
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| Secondary | Percentage of Participants With Disease Control Rate (DCR) | DCR was the percentage of the participants who had BOR of CR, PR, and SD, based on assessments by each site investigator using RECIST v1.1. The minimum duration of SD was defined as 5 weeks (or 7 weeks for Schedules 1a and 2 in the Dose Escalation Part) following the date of the first dose of study drug in order for stable disease to be considered the best overall response. The 95% CI was constructed using the method of Clopper and Pearson. DCR = CR + PR + SD | The SAS was the group of participants who received study drug and had at least 1 post-dose safety assessment. | Posted | Median | 95% Confidence Interval | percentage of participants | From date of treatment start until disease progression, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment, or up to data cutoff date (17 May 2016), for up to approximately 3 years 7 months |
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| Secondary | Percentage of Participants With Clinical Benefit Rate (CBR) | CBR was defined as the percentage of participants with BOR of CR or PR or durable stable disease (dSD) [CR + PR + dSD] based on RECIST v1.1. The dSD rate was defined as the percentage of participants with dSD (based on RECIST 1.1 and defined as SD lasting greater than or equal to 6 months), as determined by the site Investigator. | The SAS was the group of participants who received study drug and had at least 1 post-dose safety assessment. | Posted | Median | 95% Confidence Interval | percentage of participants | From date of treatment start until disease progression, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment, or up to data cutoff date (17 May 2016), for up to approximately 3 years 7 months |
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| Secondary | Percentage of Participants With Progression Free Survival (PFS) | PFS was defined as the time from the date of treatment start until progressive disease or death from any cause in the absence of progressive disease. Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions (taking as reference the smallest sum on study), recorded since the treatment started or the appearance of 1 or more new lesions as assessed by IRR using RECIST v1.1. The duration of PFS was calculated as end date minus date of first drug plus 1, based on assessments by the site Investigator. PFS was calculated using Kaplan-Meier estimate and presented with 2-sided 95% Cl. | PFS data was not collected as this is a Phase I dose escalation design and was not the focus of the study. | Posted | From date of treatment start until disease progression, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment, or up to data cutoff date (17 May 2016), for up to approximately 3 years 7 months |
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| Secondary | Number of Participants With the Indicated Shift From Baseline Category to the Indicated Worst Post-Baseline Category | The effects of eribulin-LF on cardiovascular repolarization were evaluated via 24-hour, 12-lead continuous Holter electrocardiogram (ECG) monitoring in Cycle 1, Day 1 for Schedule 1 and Day 1 and Day 15 of Schedule 2. Individual ECGs were extracted in triplicate from the Holter recordings at specified time points and were evaluated by a central laboratory. QT intervals were measured from Lead II and were corrected for heart rate (QTc) using Fridericia's (QTcF) and Bazett's (QTcB) correction factors. The primary QTc parameter was QTcF. Secondary parameters (QTcB, QT, QRS, and hazard ratio/heart rate (HR)) and waveforms (T-waves) were evaluated. BL= Baseline, PBL = post-Baseline, A,NCS = abnormal, not clinically significant, A, CS = abnormal, clinically significant | The SAS was the group of participants who received study drug and had at least 1 post-dose safety assessment. Only participants with baseline and post-baseline values were reported. | Posted | Count of Participants | Participants | Baseline (Day -1), Schedule 1 (Cycle 1 Day 1); Schedule 2 (Cycle 1 Day 1 and Day 15) |
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From date of first dose until 30 days after the final dose of study drug, up to approximately 3 years 8 months
Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) were reported for the Safety Analysis Set. All adverse events were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.1. Participants who did not receive treatment were not analyzed.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Schedule 1 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. | 0 | 7 | 1 | 7 | 7 | 7 |
| EG001 | Schedule 1 Dose Escalation Cohort: 1.4 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.4 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. | 0 | 6 | 2 | 6 | 6 | 6 |
| EG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. | 0 | 7 | 6 | 7 | 7 | 7 |
| EG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. | 0 | 3 | 1 | 3 | 3 | 3 |
| EG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. | 0 | 9 | 3 | 9 | 8 | 9 |
| EG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. | 0 | 3 | 2 | 3 | 3 | 3 |
| EG006 | Schedule 2 Expansion Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Expansion Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle. | 0 | 23 | 9 | 23 | 23 | 23 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (18.0) | Systematic Assessment |
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| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (18.0) | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA (18.0) | Systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA (18.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Device leakage | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Device occlusion | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Malaise | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Cholecystitis acute | Hepatobiliary disorders | MedDRA (18.0) | Systematic Assessment |
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| Drug hypersensitivity | Immune system disorders | MedDRA (18.0) | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Neutropenic sepsis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Pyelonephritis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Wound infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA (18.0) | Systematic Assessment |
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| Transaminases increased | Investigations | MedDRA (18.0) | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (18.0) | Systematic Assessment |
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| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (18.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
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| Spinal cord compression | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA (18.0) | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Psoriasis | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA (18.0) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (18.0) | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA (18.0) | Systematic Assessment |
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| Leukopenia | Blood and lymphatic system disorders | MedDRA (18.0) | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA (18.0) | Systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA (18.0) | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA (18.0) | Systematic Assessment |
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| Cushingoid | Endocrine disorders | MedDRA (18.0) | Systematic Assessment |
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| Dry eye | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Lip disorder | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Lip dry | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Oesophageal pain | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Paraesthesia oral | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Face oedema | General disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Infusion site erythema | General disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Suprapubic pain | General disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Hepatitis fulminant | Hepatobiliary disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Gastrointestinal bacterial infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Viral rhinitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (18.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (18.0) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (18.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (18.0) | Systematic Assessment |
| |
| Blood magnesium decreased | Investigations | MedDRA (18.0) | Systematic Assessment |
| |
| Blood magnesium increased | Investigations | MedDRA (18.0) | Systematic Assessment |
| |
| Blood uric acid increased | Investigations | MedDRA (18.0) | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA (18.0) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (18.0) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (18.0) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (18.0) | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Neurotoxicity | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Chromaturia | Renal and urinary disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Vulvovaginal pain | Reproductive system and breast disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Psoriasis | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Skin mass | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Spider naevus | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Vasodilatation | Vascular disorders | MedDRA (18.0) | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Eisai Medical Information | Eisai Inc. | 1-888-274-2378 | esi_medinfo@eisai.com |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| C490954 | eribulin |
Not provided
Not provided
Not provided
| Male |
|
| OG001 | Schedule 1 Dose Escalation Cohort: 1.4 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.4 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
|
|
| OG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG006 | Schedule 2 Expansion Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Expansion Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle. |
|
|
| Schedule 1 Dose Escalation Cohort: 1.4 mg/m^2 Eribulin-LF |
Dose Escalation Cohort: Eribulin-LF (1.4 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
|
|
Dose Escalation Cohort: Eribulin-LF (1.4 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death.
| OG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
|
|
| OG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
|
|
Dose Escalation Cohort: Eribulin-LF (1.4 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
|
|
Dose Escalation Cohort: Eribulin-LF (1.4 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death.
| OG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
|
|
Dose Escalation Cohort: Eribulin-LF (1.4 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
|
|
Dose Escalation Cohort: Eribulin-LF (1.4 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death.
| OG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
|
|
Dose Escalation Cohort: Eribulin-LF (1.4 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death.
| OG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
|
|
Dose Escalation Cohort: Eribulin-LF (1.4 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death.
| OG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
|
|
| Schedule 1 Dose Escalation Cohort: 1.4 mg/m^2 Eribulin-LF |
Dose Escalation Cohort: Eribulin-LF (1.4 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG006 | Schedule 2 Expansion Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Expansion Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle. |
|
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| OG001 | Schedule 1 Dose Escalation Cohort: 1.4 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.4 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG006 | Schedule 2 Expansion Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Expansion Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle. |
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| OG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG006 | Schedule 2 Expansion Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Expansion Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle. |
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| OG002 |
| Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF |
Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG006 | Schedule 2 Expansion Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Expansion Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle. |
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Dose Escalation Cohort: Eribulin-LF (1.4 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG002 | Schedule 1 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 of a 21-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG003 | Schedule 2 Dose Escalation Cohort: 1.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG004 | Schedule 2 Dose Escalation Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG005 | Schedule 2 Dose Escalation Cohort: 2.0 mg/m^2 Eribulin-LF | Dose Escalation Cohort: Eribulin-LF (2.0 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle starting at 1 mg/m^2 escalating until intolerable toxicity, disease progression or death. |
| OG006 | Schedule 2 Expansion Cohort: 1.5 mg/m^2 Eribulin-LF | Dose Expansion Cohort: Eribulin-LF (1.5 mg/m^2) was administered as an IV infusion on Day 1 and Day 15 of a 28-day cycle. |
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