Trial Outcomes & Findings for Study Of Eribulin (E7389) In Patients With Advanced Solid Tumors And Normal Or Reduced Hepatic Function As Per Child-Pugh System (NCT NCT00706095)
NCT ID: NCT00706095
Last Updated: 2012-03-27
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
18 participants
Primary outcome timeframe
Pre-dose (-0.5h); post-dose at 15 min, 30 min, 60 min, 2 hrs, 4 hrs, 6 hrs, 10 hrs, 24 hrs, 48 hrs, 72hrs, 96 hrs, 120 hrs and 144 hours.
Results posted on
2012-03-27
Participant Flow
This study was recruited at 2 centers in The Netherlands during the period of Feb 2008 to Jan 2010.
Participant milestones
| Measure |
E7389 1.4 mg/m^2
E7389 Intravenous injection starting dose on Day 1 is 1.4 mg/m\^2 for normal hepatic function.
|
E7389 1.1 mg/m^2
E7389 Intravenous injection starting dose on Day 1 is 1.1 mg/m\^2 for mild hepatic impairment (Child-Pugh A)
|
E7389 0.7 mg/m^2
E7389 Intravenous injection starting dose on Day 1 is 0.7 mg/m\^2 for moderate hepatic impairment (Child-Pugh B)
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
7
|
5
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
6
|
7
|
5
|
Reasons for withdrawal
| Measure |
E7389 1.4 mg/m^2
E7389 Intravenous injection starting dose on Day 1 is 1.4 mg/m\^2 for normal hepatic function.
|
E7389 1.1 mg/m^2
E7389 Intravenous injection starting dose on Day 1 is 1.1 mg/m\^2 for mild hepatic impairment (Child-Pugh A)
|
E7389 0.7 mg/m^2
E7389 Intravenous injection starting dose on Day 1 is 0.7 mg/m\^2 for moderate hepatic impairment (Child-Pugh B)
|
|---|---|---|---|
|
Overall Study
Progressive Disease
|
4
|
5
|
3
|
|
Overall Study
Clinical Progression
|
1
|
2
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
Baseline Characteristics
Study Of Eribulin (E7389) In Patients With Advanced Solid Tumors And Normal Or Reduced Hepatic Function As Per Child-Pugh System
Baseline characteristics by cohort
| Measure |
E7389 1.4 mg/m^2
n=6 Participants
E7389 Intravenous injection starting dose on Day 1 is 1.4 mg/m\^2 for normal hepatic function.
|
E7389 1.1 mg/m^2
n=7 Participants
E7389 Intravenous injection starting dose on Day 1 is 1.1 mg/m\^2 for mild hepatic impairment (Child-Pugh A)
|
E7389 0.7 mg/m^2
n=5 Participants
E7389 Intravenous injection starting dose on Day 1 is 0.7 mg/m\^2 for moderate hepatic impairment (Child-Pugh B)
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
60.2 years
STANDARD_DEVIATION 5.98 • n=5 Participants
|
59.9 years
STANDARD_DEVIATION 4.88 • n=7 Participants
|
65.2 years
STANDARD_DEVIATION 2.68 • n=5 Participants
|
61.4 years
STANDARD_DEVIATION 5.14 • n=4 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
6 participants
n=5 Participants
|
7 participants
n=7 Participants
|
5 participants
n=5 Participants
|
18 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Pre-dose (-0.5h); post-dose at 15 min, 30 min, 60 min, 2 hrs, 4 hrs, 6 hrs, 10 hrs, 24 hrs, 48 hrs, 72hrs, 96 hrs, 120 hrs and 144 hours.Population: Pharmacokinetic Population
Outcome measures
| Measure |
E7389 1.4 mg/m^2
n=6 Participants
E7389 Intravenous injection starting dose on Day 1 is 1.4 mg/m\^2 for normal hepatic function.
|
E7389 1.1 mg/m^2
n=7 Participants
E7389 Intravenous injection starting dose on Day 1 is 1.1 mg/m\^2 for mild hepatic impairment (Child-Pugh A)
|
E7389 0.7 mg/m^2
n=5 Participants
E7389 Intravenous injection starting dose on Day 1 is 0.7 mg/m\^2 for moderate hepatic impairment (Child-Pugh B)
|
|---|---|---|---|
|
Mean (SD) Pharmacokinetic (PK) Parameter Area Under Concentration Time Curve From Zero to Infinity (AUC0-oo)
|
600 ng*hr/mL
Standard Deviation 267.1
|
731 ng*hr/mL
Standard Deviation 288.3
|
720 ng*hr/mL
Standard Deviation 407.4
|
PRIMARY outcome
Timeframe: Pre-dose (-0.5h); post-dose at 15 min, 30 min, 60 min, 2 hrs, 4 hrs, 6 hrs, 10 hrs, 24 hrs, 48 hrs, 72hrs, 96 hrs, 120 hrs and 144 hours.Population: Pharmacokinetic Population
Outcome measures
| Measure |
E7389 1.4 mg/m^2
n=6 Participants
E7389 Intravenous injection starting dose on Day 1 is 1.4 mg/m\^2 for normal hepatic function.
|
E7389 1.1 mg/m^2
n=7 Participants
E7389 Intravenous injection starting dose on Day 1 is 1.1 mg/m\^2 for mild hepatic impairment (Child-Pugh A)
|
E7389 0.7 mg/m^2
n=5 Participants
E7389 Intravenous injection starting dose on Day 1 is 0.7 mg/m\^2 for moderate hepatic impairment (Child-Pugh B)
|
|---|---|---|---|
|
Mean (SD) Pharmacokinetic (PK) Parameter Maximum Observed Plasma Concentration (Cmax)
|
186 ng/mL
Standard Deviation 67.4
|
147 ng/mL
Standard Deviation 47.6
|
113 ng/mL
Standard Deviation 47.2
|
PRIMARY outcome
Timeframe: throughout the study and up to 30 days after the last dose of study drugPopulation: ITT Population
Defined as the best response from the start of treatment until disease progression or recurrence. Lesions measured by computed tomography (CT) scan and magnetic resonance imaging (MRI). Objective response rate: complete response (CR-disappearance of all lesions)+ partial response (PR-30% decrease in lesion diameter), Progressive Disease (PD-20% increase in lesion diameter), stable disease (SD-neither shrinkage nor increase of lesions).
Outcome measures
| Measure |
E7389 1.4 mg/m^2
n=6 Participants
E7389 Intravenous injection starting dose on Day 1 is 1.4 mg/m\^2 for normal hepatic function.
|
E7389 1.1 mg/m^2
n=7 Participants
E7389 Intravenous injection starting dose on Day 1 is 1.1 mg/m\^2 for mild hepatic impairment (Child-Pugh A)
|
E7389 0.7 mg/m^2
n=5 Participants
E7389 Intravenous injection starting dose on Day 1 is 0.7 mg/m\^2 for moderate hepatic impairment (Child-Pugh B)
|
|---|---|---|---|
|
Best Overall Response Per Response Evaluation Criteria in Solid Tumors (RECIST)
Best Overall Response - Complete Response
|
0 Number of Participants
|
0 Number of Participants
|
0 Number of Participants
|
|
Best Overall Response Per Response Evaluation Criteria in Solid Tumors (RECIST)
Best Overall Response - Partial Response
|
0 Number of Participants
|
0 Number of Participants
|
0 Number of Participants
|
|
Best Overall Response Per Response Evaluation Criteria in Solid Tumors (RECIST)
Best Overall Response - Stable Disease
|
4 Number of Participants
|
1 Number of Participants
|
4 Number of Participants
|
|
Best Overall Response Per Response Evaluation Criteria in Solid Tumors (RECIST)
Best Overall Response - Progressive Disease
|
2 Number of Participants
|
5 Number of Participants
|
1 Number of Participants
|
|
Best Overall Response Per Response Evaluation Criteria in Solid Tumors (RECIST)
Best Overall Response - Missing
|
0 Number of Participants
|
1 Number of Participants
|
0 Number of Participants
|
Adverse Events
E7389 1.4 mg/m^2
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
E7389 1.1 mg/m^2
Serious events: 4 serious events
Other events: 7 other events
Deaths: 0 deaths
E7389 0.7 mg/m^2
Serious events: 3 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
E7389 1.4 mg/m^2
n=6 participants at risk
E7389 Intravenous injection starting dose on Day 1 is 1.4 mg/m\^2 for normal hepatic function.
|
E7389 1.1 mg/m^2
n=7 participants at risk
E7389 Intravenous injection starting dose on Day 1 is 1.1 mg/m\^2 for mild hepatic impairment (Child-Pugh A)
|
E7389 0.7 mg/m^2
n=5 participants at risk
E7389 Intravenous injection starting dose on Day 1 is 0.7 mg/m\^2 for moderate hepatic impairment (Child-Pugh B)
|
|---|---|---|---|
|
Gastrointestinal disorders
Duodenal Obstruction
|
0.00%
0/6
|
0.00%
0/7
|
20.0%
1/5
|
|
Gastrointestinal disorders
Gastrointestinal Hemorrhage
|
0.00%
0/6
|
14.3%
1/7
|
0.00%
0/5
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/6
|
14.3%
1/7
|
0.00%
0/5
|
|
Gastrointestinal disorders
Esophageal Varices Hemorrhage
|
0.00%
0/6
|
14.3%
1/7
|
0.00%
0/5
|
|
Gastrointestinal disorders
Vomiting
|
16.7%
1/6
|
0.00%
0/7
|
0.00%
0/5
|
|
Investigations
Blood Bilirubin Increased
|
0.00%
0/6
|
0.00%
0/7
|
20.0%
1/5
|
|
Investigations
Blood Creatinine Increased
|
0.00%
0/6
|
14.3%
1/7
|
0.00%
0/5
|
|
Metabolism and nutrition disorders
Dehydration
|
16.7%
1/6
|
0.00%
0/7
|
20.0%
1/5
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Ascites
|
0.00%
0/6
|
0.00%
0/7
|
20.0%
1/5
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Neoplasm Progression
|
0.00%
0/6
|
14.3%
1/7
|
0.00%
0/5
|
|
Injury, poisoning and procedural complications
Rib Fracture
|
0.00%
0/6
|
14.3%
1/7
|
0.00%
0/5
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/6
|
0.00%
0/7
|
20.0%
1/5
|
|
Psychiatric disorders
Confusional State
|
0.00%
0/6
|
0.00%
0/7
|
20.0%
1/5
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.00%
0/6
|
14.3%
1/7
|
0.00%
0/5
|
Other adverse events
| Measure |
E7389 1.4 mg/m^2
n=6 participants at risk
E7389 Intravenous injection starting dose on Day 1 is 1.4 mg/m\^2 for normal hepatic function.
|
E7389 1.1 mg/m^2
n=7 participants at risk
E7389 Intravenous injection starting dose on Day 1 is 1.1 mg/m\^2 for mild hepatic impairment (Child-Pugh A)
|
E7389 0.7 mg/m^2
n=5 participants at risk
E7389 Intravenous injection starting dose on Day 1 is 0.7 mg/m\^2 for moderate hepatic impairment (Child-Pugh B)
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
50.0%
3/6
|
42.9%
3/7
|
40.0%
2/5
|
|
Gastrointestinal disorders
Vomiting
|
16.7%
1/6
|
57.1%
4/7
|
40.0%
2/5
|
|
Gastrointestinal disorders
Constipation
|
33.3%
2/6
|
28.6%
2/7
|
20.0%
1/5
|
|
Gastrointestinal disorders
Diarrhea
|
16.7%
1/6
|
28.6%
2/7
|
40.0%
2/5
|
|
Gastrointestinal disorders
Abdominal Pain
|
33.3%
2/6
|
0.00%
0/7
|
20.0%
1/5
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
0.00%
0/6
|
14.3%
1/7
|
40.0%
2/5
|
|
Gastrointestinal disorders
Stomatitis
|
16.7%
1/6
|
28.6%
2/7
|
0.00%
0/5
|
|
Gastrointestinal disorders
Abdominal Distention
|
0.00%
0/6
|
28.6%
2/7
|
0.00%
0/5
|
|
Gastrointestinal disorders
Dry Mouth
|
16.7%
1/6
|
14.3%
1/7
|
0.00%
0/5
|
|
Gastrointestinal disorders
Hematochezia
|
0.00%
0/6
|
14.3%
1/7
|
20.0%
1/5
|
|
Gastrointestinal disorders
Melena
|
0.00%
0/6
|
14.3%
1/7
|
20.0%
1/5
|
|
General disorders
Fatigue
|
33.3%
2/6
|
85.7%
6/7
|
60.0%
3/5
|
|
General disorders
Edema Peripheral
|
0.00%
0/6
|
14.3%
1/7
|
40.0%
2/5
|
|
General disorders
Pyrexia
|
0.00%
0/6
|
14.3%
1/7
|
20.0%
1/5
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
16.7%
1/6
|
71.4%
5/7
|
80.0%
4/5
|
|
Skin and subcutaneous tissue disorders
Rash
|
66.7%
4/6
|
14.3%
1/7
|
0.00%
0/5
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
16.7%
1/6
|
0.00%
0/7
|
60.0%
3/5
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
16.7%
1/6
|
0.00%
0/7
|
20.0%
1/5
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
16.7%
1/6
|
14.3%
1/7
|
0.00%
0/5
|
|
Musculoskeletal and connective tissue disorders
Muscular Stiffness
|
0.00%
0/6
|
14.3%
1/7
|
20.0%
1/5
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
16.7%
1/6
|
14.3%
1/7
|
0.00%
0/5
|
|
Investigations
Weight Decreased
|
16.7%
1/6
|
28.6%
2/7
|
40.0%
2/5
|
|
Investigations
Blood Bilirubin Increased
|
0.00%
0/6
|
28.6%
2/7
|
20.0%
1/5
|
|
Investigations
Aspartate Aminotransferase Increased
|
0.00%
0/6
|
14.3%
1/7
|
20.0%
1/5
|
|
Investigations
Blood Creatinine Increased
|
0.00%
0/6
|
28.6%
2/7
|
0.00%
0/5
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
16.7%
1/6
|
0.00%
0/7
|
80.0%
4/5
|
|
Nervous system disorders
Dysgeusia
|
16.7%
1/6
|
14.3%
1/7
|
20.0%
1/5
|
|
Nervous system disorders
Headache
|
16.7%
1/6
|
14.3%
1/7
|
0.00%
0/5
|
|
Nervous system disorders
Paresthesia
|
33.3%
2/6
|
0.00%
0/7
|
0.00%
0/5
|
|
Nervous system disorders
Peripheral Motor Neuropathy
|
0.00%
0/6
|
0.00%
0/7
|
40.0%
2/5
|
|
Blood and lymphatic system disorders
Neutropenia
|
16.7%
1/6
|
28.6%
2/7
|
60.0%
3/5
|
|
Blood and lymphatic system disorders
Anemia
|
16.7%
1/6
|
14.3%
1/7
|
20.0%
1/5
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/6
|
0.00%
0/7
|
40.0%
2/5
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/6
|
42.9%
3/7
|
20.0%
1/5
|
|
Metabolism and nutrition disorders
Dehydration
|
16.7%
1/6
|
0.00%
0/7
|
40.0%
2/5
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6
|
14.3%
1/7
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
16.7%
1/6
|
14.3%
1/7
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/6
|
28.6%
2/7
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal Pain
|
16.7%
1/6
|
14.3%
1/7
|
0.00%
0/5
|
|
Vascular disorders
Hypotension
|
0.00%
0/6
|
14.3%
1/7
|
20.0%
1/5
|
|
Psychiatric disorders
Confusional State
|
0.00%
0/6
|
28.6%
2/7
|
20.0%
1/5
|
Additional Information
Eisai Inc.
Eisai Call Center
Phone: 888-422-4743
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place