ESKIMO: Eribulin Mesylate Phase IV Clinical Trial in Korean Patients With Metastatic or Locally Advanced Breast Cancer

• Sponsor: Eisai Korea Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01961544
• Collaborator: (none)
• Enrollment: 101
• Locations: 14
• Arm: 1
• Duration (Months): 25
• Patients Per Site: 7.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This clinical study is designed as an open, single group, multi-center, phase 4 clinical study to assess the safety of eribulin which is approved for the treatment of the patients in Korea with locally advanced or metastatic breast cancer who had received two to five prior chemotherapy regimens including anthracyclines and taxanes for advanced disease.

Subjects who meet the inclusion/exclusion criteria are administered of 1.4 mg/m2 of the investigational product intravenously in 2-5 min on day 1 and day 8 of every 21-day cycle. In case of the progression of disease, unacceptable toxicity, withdrawal of the consent, or judgment by investigator that the treatment needs to be stopped, the treatment of investigational product is stopped, and treatment termination assessment is performed within 30 days from the last treatment.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms; Breast Cancer	Drug: Eribulin mesylate	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 101 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase IV Clinical Trial to Evaluate Safety of Eribulin in Patients With Locally Advanced or Metastatic Breast Cancer
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eribulin mesylate 1.4 mg/m2 (as eribulin 1.23 mg/m2) day by 2-5 minutes IV on Day 1 and 8 every 21 days	Drug: Eribulin mesylate; 1.4 mg/m2 (as eribulin 1.23 mg/m2) day by 2-5 minutes IV on Day 1 and 8 every 21 days

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Treatment-emergent Serious Adverse Event (SAE) [mean of 3.76 months]

   An AE is defined as any harmful, untoward sign (including abnormal laboratory value, etc.), symptom, or disease in a participant administered investigational product that does not necessarily have a causal relationship with treatment. An SAE is defined as an AE that is life threatening or results in death, results in hospitalization (initial or prolonged), results in a disability (significant, persistent, or permanent change, impairment, damage or disruption in the participant's body function/structure, physical activities, or quality of life), results in a congenital anomaly, or requires intervention to prevent permanent impairment or damage. TEAEs are defined as those events that started on or after the date and time of administration of the first dose of study drug and those events that were present prior to the administration of the first dose of study drug and increased in severity during the study.

Secondary Outcome Measures

1. Disease Control Rate (DCR) [mean of 3.76 months]

   DCR is defined as the number of participants with complete response (CR), partial response (PR), and stable disease (SD). The Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to assess the tumor response. Tumor response was evaluated by investigators. CR is defined as the disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 millimeters (mm) in the short axis. PR is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (SLD increased by at least 20% from the smallest value on study [including baseline, if that is the smallest]. The SLD must also demonstrate an absolute increase of at least 5 mm. [Two lesions increasing from 2 mm to 3 mm, for example, does not qualify]).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Female, Age greater or equal to 20 years

2. Patients with histologically or cytologically confirmed carcinoma of the breast

3. Patients with locally advance or metastatic carcinoma of the breast

4. Patients who have received two to five prior chemotherapeutic regimens including an antracycline and a taxane and 2 or more regimens for locally recurrent and/or metastatic disease

5. Patients must have proved refractory to the most recent chemotherapy on or within six (6) months of therapy

6. Patients who have assessable lesion according to RECIST v 1.1

7. Adequately maintained bone marrow function

• absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9 /L

• hemoglobin greater than or equal to 10.0 g/dl (a hemoglobin less than 10.0 g/dL is acceptable if it is corrected by erythropoietin or transfusion)

• Platelet count greater than or equal to 100 x 10^9 /L

1. Adequately maintained liver function

• Total bilirubin: less than or equal to 1.5 times the upper limits of normal (ULN) and

• Alkaline phosphatase(ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 x ULN (in the case of liver metastases less than or equal to 5 x ULN)

1. Adequately maintained renal function

• Serum creatinine less than or equal to 2.0 mg/dl or

• Calculated creatinine clearance greater than or equal to 40 ml/min (Cockcroft and Gault formula)

1. Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for

• alopecia

• stable sensory neuropathy less than or equal to Grade 2

1. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2

2. Life expectancy of greater than or equal to 3 months

3. Patients willing and able to comply with the study protocol for the duration of the study

4. Patients who have provided written consent to participate in this study

Exclusion Criteria

1. Patients who have received a chemotherapy, radiation, biologics, immunotherapy or hormonal therapy within three weeks before treatment start (but, palliative radiation can be enrolled)

2. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen

3. Patients 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 four weeks before starting treatment in this study. Any signs and/or symptoms of brain metastases must be stable for at least four weeks before starting study treatment

4. Patients with meningeal carcinomatosis

5. Significant cardiovascular impairment

• Myocardial infarction within the past six months, unstable angina, history of congestive heart failure NYHA class III or IV, or serious cardiac arrhythmia

• QTc prolongation (Bazett's Formula greater than 480 msec) or congenital long QT syndrome

1. Severe/uncontrolled intercurrent illness/infection required administration of antibiotic injection

2. Patients who have processed a major surgery within four weeks before participation in this clinical trial

3. Patients who have had a prior malignancy within the past five years other than breast cancer (but, treated non-melanoma skin cancer and carcinoma in situ of the cervix will not be excluded)

4. Patients with known positive HIV status

5. Patients who have received genetic therapy or other investigational drug within 4 weeks before treatment start or expected to receive prohibited medication

6. Patients with prior allergies to Halichondrin B, its derivatives, active ingredient, or other diluting agent

7. Patients who have received this investigational product before registration for this study

8. Patients who are pregnant, who may possibly be pregnant, or are lactating

9. Patients who do not agree to practice contraception for the study periods

10. Patients who have participated in other clinical trial within 4 weeks before screening

11. Patients otherwise judged by investigator or sub investigator to be unsuitable for inclusion

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chungbuk National University Hospital	Cheongju	Chungcheongbuk-do	Korea, Republic of	361-711
2	National Cancer Center	Goyang	Gyeonggi-do	Korea, Republic of	410-769
3	Seoul National University Bundang Hospital	Seongnam	Gyeonggi-do	Korea, Republic of	463-707
4	Ajou University Hospital	Suwon	Gyeonggi-do	Korea, Republic of	443-380
5	Dong-A University Hospital	Busan		Korea, Republic of	602-715
6	Kyungpook National University Hospital	Daegu		Korea, Republic of	700-721
7	Gachon University Gil Medical Center	Incheon		Korea, Republic of	405-760
8	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
9	Severance Hospital	Seoul		Korea, Republic of	120-752
10	Samsung Medical Center	Seoul		Korea, Republic of	135-710
11	Korea University Anam Hospital	Seoul		Korea, Republic of	136-705
12	Asan Medical Center	Seoul		Korea, Republic of	138-736
13	Korea University Guro Hospital	Seoul		Korea, Republic of	152-703
14	Ulsan University Hospital	Ulsan		Korea, Republic of	682-714

Sponsors and Collaborators

• Eisai Korea Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eisai Korea Inc.
• ClinicalTrials.gov Identifier: NCT01961544
• Other Study ID Numbers: EKI-CT-1301
• First Posted: Oct 11, 2013
• Last Update Posted: Oct 7, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Eisai Korea Inc.: Breast Cancer; Metastatic
• Additional relevant MeSH terms: Breast Neoplasms

Study Results

Participant Flow

Arm/Group Title	Eribulin Mesylate 1.4 mg/m^2
Arm/Group Description	Participants received 1.4 milligrams per meters squared (mg/m^2) eribulin mesylate intravenously over the course of 2 to 5 minutes on Day 1 and Day 8 of each 21-day cycle.
Period Title: Overall Study
STARTED	101
COMPLETED	88
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Eribulin Mesylate 1.4 mg/m^2
Arm/Group Description	Participants received 1.4 milligrams per meters squared (mg/m^2) eribulin mesylate intravenously over the course of 2 to 5 minutes on Day 1 and Day 8 of each 21-day cycle.
Overall Participants	101
Age (Years) [Geometric Mean (Standard Deviation) ]
Geometric Mean (Standard Deviation) [Years]	50.36 (10.71)
Sex: Female, Male (Count of Participants)
Female	101 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Treatment-emergent Serious Adverse Event (SAE)
Description	An AE is defined as any harmful, untoward sign (including abnormal laboratory value, etc.), symptom, or disease in a participant administered investigational product that does not necessarily have a causal relationship with treatment. An SAE is defined as an AE that is life threatening or results in death, results in hospitalization (initial or prolonged), results in a disability (significant, persistent, or permanent change, impairment, damage or disruption in the participant's body function/structure, physical activities, or quality of life), results in a congenital anomaly, or requires intervention to prevent permanent impairment or damage. TEAEs are defined as those events that started on or after the date and time of administration of the first dose of study drug and those events that were present prior to the administration of the first dose of study drug and increased in severity during the study.
Time Frame	mean of 3.76 months

Outcome Measure Data

Analysis Population Description

Safety Set: all participants who are administered investigational product at least once for the analysis

Arm/Group Title	Eribulin Mesylate 1.4 mg/m^2
Arm/Group Description	Participants received 1.4 milligrams per meters squared (mg/m^2) eribulin mesylate intravenously over the course of 2 to 5 minutes on Day 1 and Day 8 of each 21-day cycle.
Measure Participants	101
TEAE	101 100%
Treatment-emergent SAE	20 19.8%

2. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	DCR is defined as the number of participants with complete response (CR), partial response (PR), and stable disease (SD). The Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to assess the tumor response. Tumor response was evaluated by investigators. CR is defined as the disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 millimeters (mm) in the short axis. PR is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (SLD increased by at least 20% from the smallest value on study [including baseline, if that is the smallest]. The SLD must also demonstrate an absolute increase of at least 5 mm. [Two lesions increasing from 2 mm to 3 mm, for example, does not qualify]).
Time Frame	mean of 3.76 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants who were administered investigational product at least once after enrollment and had at least one primary efficacy data value since Baseline

Arm/Group Title	Eribulin Mesylate 1.4 mg/m^2
Arm/Group Description	Participants received 1.4 milligrams per meters squared (mg/m^2) eribulin mesylate intravenously over the course of 2 to 5 minutes on Day 1 and Day 8 of each 21-day cycle.
Measure Participants	96
CR	1 1%
PR	15 14.9%
SD	33 32.7%

Adverse Events

Arm/Group Title	Eribulin Mesylate 1.4 mg/m^2
Arm/Group Description	Participants received 1.4 milligrams per meters squared (mg/m^2) eribulin mesylate intravenously over the course of 2-5 minutes on Day 1 and Day 8 of each 21-day cycle.
All Cause Mortality
	Eribulin Mesylate 1.4 mg/m^2
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Eribulin Mesylate 1.4 mg/m^2
	Affected / at Risk (%)	# Events
Total	20/101 (19.8%)
Blood and lymphatic system disorders
Neutropenia	2/101 (2%)
Febrile neutropenia	1/101 (1%)
Cardiac disorders
Pericardial effusion	2/101 (2%)
Gastrointestinal disorders
Abdominal distension	1/101 (1%)
Abdominal pain	1/101 (1%)
Ascites	1/101 (1%)
Gastritis	1/101 (1%)
General disorders
Asthenia	1/101 (1%)
Pyrexia	1/101 (1%)
Infections and infestations
Pneumonia	1/101 (1%)
Pseudomonal sepsis	1/101 (1%)
Septic shock	1/101 (1%)
Subcutaneous abscess	1/101 (1%)
Injury, poisoning and procedural complications
Wound secretion	1/101 (1%)
Metabolism and nutrition disorders
Decreased appetite	1/101 (1%)
Hypophagia	1/101 (1%)
Musculoskeletal and connective tissue disorders
Pathological fracture	1/101 (1%)
Spinal pain	1/101 (1%)
Nervous system disorders
Consciousness fluctuating	1/101 (1%)
Dizziness	1/101 (1%)
Headache	1/101 (1%)
Neuropathy peripheral	1/101 (1%)
Syncope	1/101 (1%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	1/101 (1%)
Pneumonia aspiration	1/101 (1%)
Other (Not Including Serious) Adverse Events
	Eribulin Mesylate 1.4 mg/m^2
	Affected / at Risk (%)	# Events
Total	101/101 (100%)
Blood and lymphatic system disorders
Neutropenia	92/101 (91.1%)
Anaemia	12/101 (11.9%)
Leukopenia	11/101 (10.9%)
Thrombocytopenia	4/101 (4%)
Febrile neutropenia	1/101 (1%)
Cardiac disorders
Palpitations	1/101 (1%)
Ear and labyrinth disorders
Ear pain	1/101 (1%)
External ear pain	1/101 (1%)
Tinnitus	1/101 (1%)
Eye disorders
Eye pain	4/101 (4%)
Blepharitis	1/101 (1%)
Dry age-related macular degeneration	1/101 (1%)
Dry eye	1/101 (1%)
Vision blurred	1/101 (1%)
Xerophthalmia	1/101 (1%)
Gastrointestinal disorders
Nausea	25/101 (24.8%)
Vomiting	11/101 (10.9%)
Diarrhoea	10/101 (9.9%)
Dyspepsia	10/101 (9.9%)
Constipation	9/101 (8.9%)
Stomatitis	8/101 (7.9%)
Abdominal pain	5/101 (5%)
Abdominal pain upper	5/101 (5%)
Toothache	3/101 (3%)
Abdominal discomfort	2/101 (2%)
Abdominal distension	2/101 (2%)
Gastrointestinal disorder	2/101 (2%)
Dry mouth	1/101 (1%)
Epigastric discomfort	1/101 (1%)
Food poisoning	1/101 (1%)
Gastritis	1/101 (1%)
Gastrointestinal pain	1/101 (1%)
Gastrooesophageal reflux disease	1/101 (1%)
Gingival bleeding	1/101 (1%)
Mouth ulceration	1/101 (1%)
General disorders
Fatigue	27/101 (26.7%)
Pyrexia	17/101 (16.8%)
Chest pain	10/101 (9.9%)
Asthenia	8/101 (7.9%)
Mucosal inflammation	8/101 (7.9%)
Pain	7/101 (6.9%)
Chills	5/101 (5%)
Influenza like illness	4/101 (4%)
Oedema peripheral	2/101 (2%)
Peripheral swelling	2/101 (2%)
Application site pain	1/101 (1%)
Face oedema	1/101 (1%)
Localised oedema	1/101 (1%)
Non-cardiac chest pain	1/101 (1%)
Oedema	1/101 (1%)
Infections and infestations
Nasopharyngitis	7/101 (6.9%)
Upper respiratory tract infection	6/101 (5.9%)
Urinary tract infection	3/101 (3%)
Cystitis	2/101 (2%)
Herpes zoster	2/101 (2%)
Pneumonia	2/101 (2%)
Device related infection	1/101 (1%)
Infection	1/101 (1%)
Paronychia	1/101 (1%)
Pyuria	1/101 (1%)
Injury, poisoning and procedural complications
Eye injury	1/101 (1%)
Investigations
Aspartate aminotransferase increased	8/101 (7.9%)
Alanine aminotransferase increased	5/101 (5%)
Electrocardiogram QT prolonged	2/101 (2%)
Haemoglobin decreased	1/101 (1%)
Blood creatinine increased	1/101 (1%)
Neutrophil count increased	1/101 (1%)
Weight decreased	1/101 (1%)
White blood cell count increased	1/101 (1%)
Metabolism and nutrition disorders
Decreased appetite	41/101 (40.6%)
Hyperglycaemia	4/101 (4%)
Hypoglycaemia	1/101 (1%)
Hypercalcaemia	1/101 (1%)
Hypoalbuminaemia	1/101 (1%)
Hypokalaemia	1/101 (1%)
Hypomagnesaemia	1/101 (1%)
Musculoskeletal and connective tissue disorders
Myalgia	25/101 (24.8%)
Back pain	6/101 (5.9%)
Pain in extremity	4/101 (4%)
Flank pain	4/101 (4%)
Muscular weakness	3/101 (3%)
Musculoskeletal pain	2/101 (2%)
Arthralgia	1/101 (1%)
Arthritis	1/101 (1%)
Bone pain	1/101 (1%)
Musculoskeletal chest pain	1/101 (1%)
Musculoskeletal discomfort	1/101 (1%)
Neck pain	1/101 (1%)
Osteonecrosis of jaw	1/101 (1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage	1/101 (1%)
Nervous system disorders
Peripheral sensory neuropathy	16/101 (15.8%)
Headache	12/101 (11.9%)
Neuropathy peripheral	11/101 (10.9%)
Dizziness	7/101 (6.9%)
Lethargy	4/101 (4%)
Hypoaesthesia	3/101 (3%)
Paraesthesia	2/101 (2%)
Dysgeusia	1/101 (1%)
Hemiparesis	1/101 (1%)
Peripheral motor neuropathy	1/101 (1%)
Psychiatric disorders
Insomnia	8/101 (7.9%)
Depression	3/101 (3%)
Anxiety	2/101 (2%)
Eating disorder symptom	1/101 (1%)
Renal and urinary disorders
Dysuria	2/101 (2%)
Haematuria	1/101 (1%)
Oliguria	1/101 (1%)
Reproductive system and breast disorders
Pelvic pain	3/101 (3%)
Vaginal haemorrhage	3/101 (3%)
Breast pain	2/101 (2%)
Respiratory, thoracic and mediastinal disorders
Cough	19/101 (18.8%)
Dyspnoea	10/101 (9.9%)
Oropharyngeal pain	5/101 (5%)
Productive cough	5/101 (5%)
Rhinorrhoea	2/101 (2%)
Dysphonia	1/101 (1%)
Dyspnoea exertional	1/101 (1%)
Nasal obstruction	1/101 (1%)
Pleural effusion	1/101 (1%)
Pulmonary embolism	1/101 (1%)
Skin and subcutaneous tissue disorders
Alopecia	46/101 (45.5%)
Rash	6/101 (5.9%)
Pruritus	5/101 (5%)
Hyperhidrosis	1/101 (1%)
Pruritus generalised	1/101 (1%)
Rash erythematous	1/101 (1%)
Vascular disorders
Lymphoedema	2/101 (2%)
Embolism	1/101 (1%)
Flushing	1/101 (1%)
Hypotension	1/101 (1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.