A Randomized, Open-label, Multicenter, Phase 3 Study to Compare the Efficacy and Safety of Eribulin With Treatment of Physician's Choice in Subjects With Advanced Non-Small Cell Lung Cancer

• Sponsor: Eisai Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01454934
• Collaborator: (none)
• Enrollment: 540
• Locations: 84
• Arms: 2
• Actual Duration (Months): 52.8
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a randomized, open-label, multicenter, Phase 3 study, comparing efficacy and safety of eribulin with TPC in subjects with advanced and disease progression following at least two prior regimens for advanced disease, which should have included a platinum-based regimen.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer (NSCLC)	Drug: Eribulin; Drug: TPC -Vinorelbine,Gemcitabine,Docetaxel, and Pemetrexed	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 540 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Actual Study Start Date: Dec 9, 2011
• Actual Primary Completion Date: May 30, 2014
• Actual Study Completion Date: May 2, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A	Drug: Eribulin; Administration of eribulin mesylate at a dose of 1.4 mg/m2 i.v. over 2 to 5 minutes on Days 1 and Day 8 of every cycle, where the duration of each cycle is 21 days.
Active Comparator: Arm B	Drug: TPC -Vinorelbine,Gemcitabine,Docetaxel, and Pemetrexed; Vinorelbine 30 mg/m2 i.v. on Day 1, every 7 days Gemcitabine 1250 mg/m2 i.v. on Days 1 and 8, every 21 days Docetaxel 75 mg/m2 i.v. on Day 1 every 21 days Pemetrexed 500 mg/m2 i.v. on Day 1 every 21 days (nonsquamous histology only).

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [Randomization (Day 1) until date of death from any cause, or 37 months]

   The OS was defined as the time in months from the date of randomization to the date of death, regardless of cause. In the absence of confirmation of death, the participants were censored either at the date that participant was last known to be alive or the date of study cut-off, whichever was earlier. The two treatment arms were compared using the log-rank test, stratified by histology, TPC option, and geographic region; and the treatment difference between eribulin mesylate and TPC was tested at a significance level of 0.05 (2-sided). Kaplan-Meier (K-M) survival probabilities for each arm were plotted over time. The treatment effect was estimated by fitting a Cox Proportional Hazards model to the OS times including treatment arm as a factor and histology, TPC option and geographic region as strata.

Secondary Outcome Measures

1. Progression Free Survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST) [Randomization (Day 1) until date of disease progression or death (whichever occurred first), or 37 months]

   PFS was defined as the time from the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first. The difference in PFS (based on the tumor response evaluation as determined by the investigator) between eribulin mesylate and TPC was evaluated using the log rank test, stratified by histology, TPC option, and geographic region, tested at an alpha level of 0.05 (2-sided). PFS censoring rules will be defined in the SAP and follow Federal Department of Agriculture (FDA) guidance.

2. Objective Response Rate (ORR) [Randomization (Day 1) to CR or PR]

   The ORR was defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) per RECIST criteria. The ORR was estimated by study arm based on the tumor response evaluation as determined by the investigator, according to RECIST 1.1. Participants with unknown response were treated as non-responders. The statistical difference in ORR between treatment arms was evaluated using the Cochran-Mantel-Haenszel (CMH) chi-square test with histology, TPC option, and geographic region as strata, tested at an alpha level of 0.05 (2-sided). The 95 percent confidence interval (CI) was calculated using Clopper Pearson method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion:

Subjects must meet all of the following criteria to be included in this study:

1. Histologically or cytologically confirmed diagnosis of NSCLC.

2. Documented evidence of advanced NSCLC not amenable to surgery or radiotherapy.

3. Confirmation of the presence or absence of EGFR mutations prior to study enrolment in all subjects.

4. Subjects must have received at least two prior regimens for advanced NSCLC, which should have included a platinum-based regimen and, in all subjects with tumors harbouring EGFR mutations, an EGFR TKI.

5. Radiographic evidence of disease progression on, or after, the last anti-cancer regimen prior to study entry.

6. Presence of measurable disease.

7. ECOG performance status of 0, 1, or 2.

8. Adequate bone marrow

9. Adequate renal function.

10. Adequate liver function.

11. Female subjects of child-bearing potential must agree to use two forms of highly effective contraception.

12. Male subjects and their female partners who are of child-bearing potential must agree to use two forms of highly effective contraception.

13. Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.

14. Males or females aged at least 18 years (or any age greater than 18 years as determined by country legislation) at the time of informed consent.

Exclusion:

Subjects who meet any of the following criteria will be excluded from this study:

1. Subjects who have received any anti-cancer therapy within 14 days, or five half-lives of the drug (whichever is longer), prior to randomization.

2. Subjects who have not recovered from toxicities as a result of prior anti-cancer therapy to less than Grade 2.

3. Subjects who have previously been treated, or participated in a study with eribulin, whether treated with eribulin or not. The TPC option must not include the same agent which the subject received in a prior regimen.

4. Peripheral neuropathy more than CTCAE Grade 2.

5. Significant cardiovascular impairment.

6. Subjects with a high probability of Long QT Syndrome, or QTc interval >500 ms.

7. Subjects with brain or subdural metastases are not eligible, unless the metastases are asymptomatic and do not require treatment or have been adequately treated by local therapy.

8. Any serious concomitant illness.

9. Known HIV positive, or have an infection requiring treatment.

10. Any malignancy that required treatment, or has shown evidence of recurrence (except for NSCLC, non-melanoma skin cancer, or histologically confirmed complete excision of carcinoma in-situ) during the 5 years prior to study entry.

11. Female subjects must not be pregnant, and must not be breastfeeding.

12. Hypersensitivity to either HalB or HalB chemical derivatives or both, or to any of the excipients of the eribulin formulation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Los Angeles	California	United States
2		Pleasant Hill	California	United States
3		San Diego	California	United States
4		Aurora	Colorado	United States
5		Washington	District of Columbia	United States
6		Port Saint Lucie	Florida	United States
7		Decatur	Illinois	United States
8		Southfield	Michigan	United States
9		Lebanon	New Hampshire	United States
10		Lake Success	New York	United States
11		Portland	Oregon	United States
12		Spokane	Washington	United States
13		Madison	Wisconsin	United States
14		Herston	Queensland	Australia
15		Frankston	Victoria	Australia
16		Strasbourg	Bas Rhin	France
17		Marseille Cedex 20	Bouches-du-Rhone	France
18		Marseille Cedex 9	Bouches-duRhone	France
19		Bordeaux	Gironde	France
20		Toulouse Cedex 9	Haute Garonne	France
21		Limoges	Haute Vienne	France
22		Rennes Cedex 9	Ille Et Vilaine	France
23		Saint Herblain	Loire Atlantique	France
24		Lille	Nord	France
25		Paris Cedex 12	Paris	France
26		Pierre Benite cedex	Rhone	France
27		Villejuif cedex	Val De Marne	France
28		Aschaffenburg	Bayern	Germany
29		Gauting	Bayern	Germany
30		Muenchen	Bayern	Germany
31		Essen	Nordrhein Westfalen	Germany
32		Koeln	Nordrhein Westfalen	Germany
33		Recklinghausen	Nordrhein Westfalen	Germany
34		Mainz	Rheinland Pfalz	Germany
35		Halle	Sachsen Anhalt	Germany
36		Hong Kong		Hong Kong
37		Lido di Camaiore	Lucca	Italy
38		Monza	Milano	Italy
39		Aviano	Pordenone	Italy
40		Cremona		Italy
41		Milano		Italy
42		Siena		Italy
43		Nagoya-shi	Aichi-Ken	Japan
44		Kashiwa-shi	Chiba-Ken	Japan
45		Fukuoka-shi	Fukuoka-Ken	Japan
46		Hiroshima-shi	Hiroshima-Ken	Japan
47		Sapporo-shi	Hokkaido	Japan
48		Kobe-shi	Hygo-Ken	Japan
49		Akashi-shi	Hyogo-ken	Japan
50		Sendai-shi	Miyagi-Ken	Japan
51		Nigata-shi	Nigata-Ken	Japan
52		Kurashiki-shi	Okayama-Ken	Japan
53		Habinko-shi	Osaka-Fu	Japan
54		Osaka-shi	Osaka-Fu	Japan
55		Osakasayama-shi	Osaka-Fu	Japan
56		Sunto-gun	Shizuoka-Ken	Japan
57		Chuo-ku	Tokyo-to	Japan
58		Koto-ku	Tokyo-To	Japan
59		Ube-shi	Yamaguchi-Ken	Japan
60		Kitaadachi-gun		Japan
61		Seongnam-si	Gyeonggi-do	Korea, Republic of
62		Suwon	Gyeonggi-do	Korea, Republic of
63		Seoul	Korea	Korea, Republic of
64		Gdansk		Poland
65		Mrozy		Poland
66		Otwock		Poland
67		Sczedin		Poland
68		Warsazawa		Poland
69		Barnaul		Russian Federation
70		Novosibirsk		Russian Federation
71		Saint Petersburg		Russian Federation
72		Singapore		Singapore
73		Sabadell	Barcelona	Spain
74		Terrassa	Barcelona	Spain
75		Pamplona	Navarra	Spain
76		Barcelona		Spain
77		Madrid		Spain
78		Taichung		Taiwan
79		Tainan		Taiwan
80		Taipei City		Taiwan
81		Taipei		Taiwan
82		London	Greater London	United Kingdom
83		Manchester	Greater Manchester	United Kingdom
84		Sutton	Surrey	United Kingdom

Sponsors and Collaborators

• Eisai Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eisai Inc.
• ClinicalTrials.gov Identifier: NCT01454934
• Other Study ID Numbers: E7389-G000-302
• First Posted: Oct 19, 2011
• Last Update Posted: Jun 26, 2019
• Last Verified: Aug 1, 2017

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Gemcitabine; Docetaxel; Pemetrexed; Vinorelbine

Study Results

Participant Flow

Pre-assignment Detail	A total of 735 participants were screened. Of these, 195 screen failed due to failure to meet inclusion/exclusion criteria, adverse events, withdrawal of consent, or other reason and were not randomized into the study. A total of 540 participants were randomized into the study. Of these, 3 were discontinued prior to treatment.

Arm/Group Title	Arm A: Eribulin Mesylate	Arm B: Vinorelbine, Gemcitabine, Docetaxel, or Pemetrexed
Arm/Group Description	Eribulin mesylate (1.4 milligram per square meter [mg/m^2]) was administered intravenously (IV) over 2 to 5 minutes on Day 1 and Day 8 of every cycle, where the duration of each cycle is 21 days.	Treatment of Physician's Choice (TPC): Vinorelbine (30 mg/m^2) was administered IV on Day 1 every 7 days, Gemcitabine (1250 mg/m^2) was administered IV on Days 1 and 8 every 21 days (or 1000 mg/m^2 IV on Days 1, 8, and 15 every 28 days), Docetaxel (75 mg/m^2) was administered IV on Day 1 every 21 days, or Pemetrexed (500 mg/m^2) was administered IV on Day 1 every 21 days (nonsquamous histology only).
Period Title: Overall Study
STARTED	270	270
COMPLETED	0	0
NOT COMPLETED	270	270

Baseline Characteristics

Arm/Group Title	Arm A: Eribulin Mesylate	Arm B: Vinorelbine, Gemcitabine, Docetaxel, or Pemetrexed	Total
Arm/Group Description	Eribulin mesylate (1.4 mg/m^2) was administered IV over 2 to 5 minutes on Day 1 and Day 8 of every cycle, where the duration of each cycle is 21 days.	TPC: Vinorelbine (30 mg/m^2) was administered IV on Day 1 every 7 days, Gemcitabine (1250 mg/m^2) was administered IV on Days 1 and 8 every 21 days (or 1000 mg/m^2 IV on Days 1, 8, and 15 every 28 days), Docetaxel (75 mg/m^2) was administered IV on Day 1 every 21 days, or Pemetrexed (500 mg/m^2) was administered IV on Day 1 every 21 days (nonsquamous histology only).	Total of all reporting groups
Overall Participants	270	270	540
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.4 (9.62)	60.8 (9.32)	61.1 (9.47)
Sex: Female, Male (Count of Participants)
Female	107 39.6%	101 37.4%	208 38.5%
Male	163 60.4%	169 62.6%	332 61.5%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	The OS was defined as the time in months from the date of randomization to the date of death, regardless of cause. In the absence of confirmation of death, the participants were censored either at the date that participant was last known to be alive or the date of study cut-off, whichever was earlier. The two treatment arms were compared using the log-rank test, stratified by histology, TPC option, and geographic region; and the treatment difference between eribulin mesylate and TPC was tested at a significance level of 0.05 (2-sided). Kaplan-Meier (K-M) survival probabilities for each arm were plotted over time. The treatment effect was estimated by fitting a Cox Proportional Hazards model to the OS times including treatment arm as a factor and histology, TPC option and geographic region as strata.
Time Frame	Randomization (Day 1) until date of death from any cause, or 37 months

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants.

Arm/Group Title	Arm A: Eribulin Mesylate	Arm B: Vinorelbine, Gemcitabine, Docetaxel, or Pemetrexed
Arm/Group Description	Eribulin mesylate (1.4 mg/m^2) was administered IV over 2 to 5 minutes on Day 1 and Day 8 of every cycle, where the duration of each cycle is 21 days.	TPC: Vinorelbine (30 mg/m^2) was administered IV on Day 1 every 7 days, Gemcitabine (1250 mg/m^2) was administered IV on Days 1 and 8 every 21 days (or 1000 mg/m^2 IV on Days 1, 8, and 15 every 28 days), Docetaxel (75 mg/m^2) was administered IV on Day 1 every 21 days, or Pemetrexed (500 mg/m^2) was administered IV on Day 1 every 21 days (nonsquamous histology only).
Measure Participants	270	270
Median (95% Confidence Interval) [months]	9.5	9.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Eribulin Mesylate, Arm B: Vinorelbine, Gemcitabine, Docetaxel, or Pemetrexed
	Comments	OS was compared between eribulin and TPC testing the following null hypothesis: H0: OS in Arm A (eribulin) is equal to OS in Arm B (TPC) against the alternative: H1: OS in Arm A (eribulin) is not equal to OS in Arm B (TPC).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1343
	Comments	P-value was calculated from a 2-sided long-rank test stratified by histology, TPC option, and geographic region.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95%; 0.95 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard Ratio was based on a Cox regression model including treatment as covariate, and histology, TPC option and geographic region as strata.

2. Secondary Outcome

Title	Progression Free Survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST)
Description	PFS was defined as the time from the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first. The difference in PFS (based on the tumor response evaluation as determined by the investigator) between eribulin mesylate and TPC was evaluated using the log rank test, stratified by histology, TPC option, and geographic region, tested at an alpha level of 0.05 (2-sided). PFS censoring rules will be defined in the SAP and follow Federal Department of Agriculture (FDA) guidance.
Time Frame	Randomization (Day 1) until date of disease progression or death (whichever occurred first), or 37 months

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants.

Arm/Group Title	Arm A: Eribulin Mesylate	Arm B: Vinorelbine, Gemcitabine, Docetaxel, or Pemetrexed
Arm/Group Description	Eribulin mesylate (1.4 mg/m^2) was administered IV over 2 to 5 minutes on Day 1 and Day 8 of every cycle, where the duration of each cycle is 21 days.	TPC: Vinorelbine (30 mg/m^2) was administered IV on Day 1 every 7 days, Gemcitabine (1250 mg/m^2) was administered IV on Days 1 and 8 every 21 days (or 1000 mg/m^2 IV on Days 1, 8, and 15 every 28 days), Docetaxel (75 mg/m^2) was administered IV on Day 1 every 21 days, or Pemetrexed (500 mg/m^2) was administered IV on Day 1 every 21 days (nonsquamous histology only).
Measure Participants	270	270
Median (95% Confidence Interval) [months]	3.0	2.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Eribulin Mesylate, Arm B: Vinorelbine, Gemcitabine, Docetaxel, or Pemetrexed
	Comments	OS was compared between eribulin and TPC testing the following null hypothesis: H0: OS in Arm A (eribulin) is equal to OS in Arm B (TPC) against the alternative: H1: OS in Arm A (eribulin) is not equal to OS in Arm B (TPC).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3946
	Comments	P-value was calculated from a 2-sided long-rank test stratified by histology, TPC option, and geographic region.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio was based on a Cox regression model including treatment as covariate, and histology, TPC option, and geographic region as strata.

3. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	The ORR was defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) per RECIST criteria. The ORR was estimated by study arm based on the tumor response evaluation as determined by the investigator, according to RECIST 1.1. Participants with unknown response were treated as non-responders. The statistical difference in ORR between treatment arms was evaluated using the Cochran-Mantel-Haenszel (CMH) chi-square test with histology, TPC option, and geographic region as strata, tested at an alpha level of 0.05 (2-sided). The 95 percent confidence interval (CI) was calculated using Clopper Pearson method.
Time Frame	Randomization (Day 1) to CR or PR

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants.

Arm/Group Title	Arm A: Eribulin Mesylate	Arm B: Vinorelbine, Gemcitabine, Docetaxel, or Pemetrexed
Arm/Group Description	Eribulin mesylate (1.4 mg/m^2) was administered IV over 2 to 5 minutes on Day 1 and Day 8 of every cycle, where the duration of each cycle is 21 days.	TPC: Vinorelbine (30 mg/m^2) was administered IV on Day 1 every 7 days, Gemcitabine (1250 mg/m^2) was administered IV on Days 1 and 8 every 21 days (or 1000 mg/m^2 IV on Days 1, 8, and 15 every 28 days), Docetaxel (75 mg/m^2) was administered IV on Day 1 every 21 days, or Pemetrexed (500 mg/m^2) was administered IV on Day 1 every 21 days (nonsquamous histology only).
Measure Participants	270	270
Number (95% Confidence Interval) [percentage of participants]	12.2 4.5%	15.2 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Eribulin Mesylate, Arm B: Vinorelbine, Gemcitabine, Docetaxel, or Pemetrexed
	Comments	OS was compared between eribulin and TPC testing the following null hypothesis: H0: OS in Arm A (eribulin) is equal to OS in Arm B (TPC) against the alternative: H1: OS in Arm A (eribulin) is not equal to OS in Arm B (TPC).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3034
	Comments	The P-value was stratified by histology, TPC option, and geographic region.
	Method	Cochran-Mantel-Haenszel
	Comments

Adverse Events

Time Frame	Treatment-emergent adverse events (AEs) and serious adverse events (SAEs) were collected from the first dose of study treatment to thirty days after final dose of study medication. Participants were followed for approximately 37 months.
Adverse Event Reporting Description	Safety analysis set included all randomized participants who received at least one dose of study treatment. AEs were graded on a 5-point scale according to Common Terminology for Adverse Events (CTCAE) version 4.0. All AEs graded 4 or 5 were considered serious.
Arm/Group Title	Arm A: Eribulin Mesylate		Arm B: Vinorelbine, Gemcitabine, Docetaxel, or Pemetrexed
Arm/Group Description	Eribulin mesylate (1.4 mg/m^2) was administered IV over 2 to 5 minutes on Day 1 and Day 8 of every cycle, where the duration of each cycle is 21 days.		TPC: Vinorelbine (30 mg/m^2) was administered IV on Day 1 every 7 days, Gemcitabine (1250 mg/m^2) was administered IV on Days 1 and 8 every 21 days (or 1000 mg/m^2 IV on Days 1, 8, and 15 every 28 days), Docetaxel (75 mg/m^2) was administered IV on Day 1 every 21 days, or Pemetrexed (500 mg/m^2) was administered IV on Day 1 every 21 days (nonsquamous histology only).
All Cause Mortality
	Arm A: Eribulin Mesylate		Arm B: Vinorelbine, Gemcitabine, Docetaxel, or Pemetrexed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/269 (10.4%)		21/268 (7.8%)
Serious Adverse Events
	Arm A: Eribulin Mesylate		Arm B: Vinorelbine, Gemcitabine, Docetaxel, or Pemetrexed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	96/269 (35.7%)		86/268 (32.1%)
Blood and lymphatic system disorders
Anaemia	2/269 (0.7%)		2/268 (0.7%)
Febrile bone marrow aplasia	1/269 (0.4%)		0/268 (0%)
Febrile neutropenia	3/269 (1.1%)		7/268 (2.6%)
Leukocytosis	1/269 (0.4%)		0/268 (0%)
Leukopenia	1/269 (0.4%)		1/268 (0.4%)
Neutropenia	4/269 (1.5%)		3/268 (1.1%)
Cardiac disorders
Acute coronary syndrome	0/269 (0%)		1/268 (0.4%)
Angina unstable	1/269 (0.4%)		0/268 (0%)
Atrial fibrillation	1/269 (0.4%)		1/268 (0.4%)
Cardiac failure	1/269 (0.4%)		0/268 (0%)
Coronary artery thrombosis	1/269 (0.4%)		0/268 (0%)
Myocardial ischaemia	2/269 (0.7%)		0/268 (0%)
Supraventricular tachycardia	1/269 (0.4%)		0/268 (0%)
Eye disorders
Cataract	1/269 (0.4%)		0/268 (0%)
Gastrointestinal disorders
Abdominal pain	1/269 (0.4%)		2/268 (0.7%)
Constipation	1/269 (0.4%)		1/268 (0.4%)
Diarrhoea	2/269 (0.7%)		1/268 (0.4%)
Dysphagia	0/269 (0%)		1/268 (0.4%)
Gastric ulcer	1/269 (0.4%)		0/268 (0%)
Gastritis	1/269 (0.4%)		0/268 (0%)
Ileus	0/269 (0%)		1/268 (0.4%)
Intestinal obstruction	0/269 (0%)		1/268 (0.4%)
Large intestinal obstruction	1/269 (0.4%)		0/268 (0%)
Nausea	0/269 (0%)		1/268 (0.4%)
Oesophageal stenosis	0/269 (0%)		1/268 (0.4%)
Oesophageal varices haemorrhage	1/269 (0.4%)		0/268 (0%)
Stomatitis	0/269 (0%)		1/268 (0.4%)
Vomiting	0/269 (0%)		1/268 (0.4%)
General disorders
Asthenia	2/269 (0.7%)		3/268 (1.1%)
Chest pain	0/269 (0%)		1/268 (0.4%)
Device failure	0/269 (0%)		1/268 (0.4%)
Face oedema	0/269 (0%)		1/268 (0.4%)
Fatigue	0/269 (0%)		3/268 (1.1%)
General physical health deterioration	13/269 (4.8%)		12/268 (4.5%)
Non-cardiac chest pain	2/269 (0.7%)		1/268 (0.4%)
Pain	1/269 (0.4%)		0/268 (0%)
Pyrexia	3/269 (1.1%)		3/268 (1.1%)
Hepatobiliary disorders
Hepatic cirrhosis	1/269 (0.4%)		0/268 (0%)
Immune system disorders
Hypersensitivity	0/269 (0%)		1/268 (0.4%)
Infections and infestations
Bronchitis	0/269 (0%)		2/268 (0.7%)
Bronchopneumonia	1/269 (0.4%)		1/268 (0.4%)
Cellulitis	1/269 (0.4%)		0/268 (0%)
Escherichia sepsis	0/269 (0%)		1/268 (0.4%)
Gastroenteritis	1/269 (0.4%)		0/268 (0%)
Herpes zoster	0/269 (0%)		1/268 (0.4%)
Lower respiratory tract infection	1/269 (0.4%)		0/268 (0%)
Lung abscess	0/269 (0%)		1/268 (0.4%)
Lung infection	2/269 (0.7%)		1/268 (0.4%)
Neutropenic sepsis	2/269 (0.7%)		2/268 (0.7%)
Oral candidiasis	1/269 (0.4%)		0/268 (0%)
Pneumonia	12/269 (4.5%)		5/268 (1.9%)
Pseudomembranous colitis	1/269 (0.4%)		0/268 (0%)
Respiratory tract infection	2/269 (0.7%)		3/268 (1.1%)
Sepsis	1/269 (0.4%)		2/268 (0.7%)
Septic shock	1/269 (0.4%)		0/268 (0%)
Staphylococcal sepsis	0/269 (0%)		1/268 (0.4%)
Upper respiratory tract infection	0/269 (0%)		1/268 (0.4%)
Urinary tract infection	1/269 (0.4%)		0/268 (0%)
Wound infection fungal	1/269 (0.4%)		0/268 (0%)
Injury, poisoning and procedural complications
Cervical vertebral fracture	1/269 (0.4%)		0/268 (0%)
Ilium fracture	1/269 (0.4%)		0/268 (0%)
Lumbar vertebral fracture	0/269 (0%)		1/268 (0.4%)
Toxicity to various agents	1/269 (0.4%)		0/268 (0%)
Investigations
Blood phosphorus decreased	0/269 (0%)		1/268 (0.4%)
Neutrophil count decreased	1/269 (0.4%)		2/268 (0.7%)
White blood cell count decreased	0/269 (0%)		1/268 (0.4%)
Metabolism and nutrition disorders
Decreased appetite	1/269 (0.4%)		3/268 (1.1%)
Diabetic ketoacidosis	0/269 (0%)		1/268 (0.4%)
Hypercalcaemia	4/269 (1.5%)		1/268 (0.4%)
Hyponatraemia	0/269 (0%)		1/268 (0.4%)
Polydipsia	1/269 (0.4%)		0/268 (0%)
Dehydration	1/269 (0.4%)		0/268 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/269 (0.4%)		0/268 (0%)
Back pain	1/269 (0.4%)		0/268 (0%)
Bone pain	1/269 (0.4%)		0/268 (0%)
Flank pain	1/269 (0.4%)		0/268 (0%)
Muscular weakness	1/269 (0.4%)		0/268 (0%)
Musculoskeletal chest pain	1/269 (0.4%)		1/268 (0.4%)
Musculoskeletal pain	0/269 (0%)		1/268 (0.4%)
Pain in extremity	0/269 (0%)		2/268 (0.7%)
Pathological fracture	1/269 (0.4%)		0/268 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	0/269 (0%)		1/268 (0.4%)
Malignant ascites	0/269 (0%)		1/268 (0.4%)
Malignant neoplasm progression	0/269 (0%)		1/268 (0.4%)
Malignant pleural effusion	1/269 (0.4%)		4/268 (1.5%)
Metastases to central nervous system	2/269 (0.7%)		0/268 (0%)
Metastases to meninges	1/269 (0.4%)		0/268 (0%)
Metastatic pain	2/269 (0.7%)		1/268 (0.4%)
Nervous system disorders
Brain oedema	1/269 (0.4%)		0/268 (0%)
Cerebral infarction	1/269 (0.4%)		0/268 (0%)
Cerebrovascular accident	1/269 (0.4%)		1/268 (0.4%)
Coma	0/269 (0%)		1/268 (0.4%)
Seizure	1/269 (0.4%)		0/268 (0%)
Dizziness	0/269 (0%)		1/268 (0.4%)
Embolic cerebral infarction	1/269 (0.4%)		0/268 (0%)
Headache	1/269 (0.4%)		0/268 (0%)
Hypoaesthesia	1/269 (0.4%)		0/268 (0%)
Monoplegia	1/269 (0.4%)		0/268 (0%)
Syncope	1/269 (0.4%)		1/268 (0.4%)
Transient ischaemic attack	0/269 (0%)		1/268 (0.4%)
Hydrocephalus	0/269 (0%)		1/268 (0.4%)
Psychiatric disorders
Confusional state	2/269 (0.7%)		0/268 (0%)
Fear	0/269 (0%)		1/268 (0.4%)
Renal and urinary disorders
Haematuria	0/269 (0%)		1/268 (0.4%)
Acute kidney injury	1/269 (0.4%)		0/268 (0%)
Reproductive system and breast disorders
Pelvic pain	0/269 (0%)		1/268 (0.4%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/269 (0.4%)		0/268 (0%)
Chronic obstructive pulmonary disease	2/269 (0.7%)		0/268 (0%)
Cough	1/269 (0.4%)		0/268 (0%)
Dyspnoea	9/269 (3.3%)		10/268 (3.7%)
Dyspnoea exertional	0/269 (0%)		1/268 (0.4%)
Haemoptysis	2/269 (0.7%)		1/268 (0.4%)
Hypoxia	1/269 (0.4%)		0/268 (0%)
Pharyngeal inflammation	1/269 (0.4%)		0/268 (0%)
Pleural effusion	2/269 (0.7%)		2/268 (0.7%)
Pneumonitis	1/269 (0.4%)		0/268 (0%)
Pneumothorax	1/269 (0.4%)		0/268 (0%)
Pulmonary embolism	2/269 (0.7%)		6/268 (2.2%)
Pulmonary hypertension	1/269 (0.4%)		0/268 (0%)
Respiratory disorder	1/269 (0.4%)		0/268 (0%)
Respiratory distress	1/269 (0.4%)		0/268 (0%)
Respiratory failure	1/269 (0.4%)		2/268 (0.7%)
Vascular disorders
Deep vein thrombosis	1/269 (0.4%)		1/268 (0.4%)
Hypotension	0/269 (0%)		1/268 (0.4%)
Jugular vein thrombosis	1/269 (0.4%)		2/268 (0.7%)
Superior vena cava syndrome	0/269 (0%)		2/268 (0.7%)
Superior vena cava stenosis	1/269 (0.4%)		0/268 (0%)
Venous thrombosis limb	1/269 (0.4%)		0/268 (0%)
Other (Not Including Serious) Adverse Events
	Arm A: Eribulin Mesylate		Arm B: Vinorelbine, Gemcitabine, Docetaxel, or Pemetrexed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	254/269 (94.4%)		261/268 (97.4%)
Blood and lymphatic system disorders
Anaemia	59/269 (21.9%)		72/268 (26.9%)
Leukopenia	27/269 (10%)		28/268 (10.4%)
Neutropenia	92/269 (34.2%)		74/268 (27.6%)
Gastrointestinal disorders
Abdominal Pain	13/269 (4.8%)		19/268 (7.1%)
Abdominal Pain Upper	17/269 (6.3%)		17/268 (6.3%)
Constipation	63/269 (23.4%)		63/268 (23.5%)
Diarrhoea	38/269 (14.1%)		45/268 (16.8%)
Nausea	73/269 (27.1%)		78/268 (29.1%)
Stomatitis	43/269 (16%)		34/268 (12.7%)
Vomiting	29/269 (10.8%)		38/268 (14.2%)
General disorders
Asthenia	59/269 (21.9%)		56/268 (20.9%)
Fatigue	66/269 (24.5%)		62/268 (23.1%)
Malaise	22/269 (8.2%)		29/268 (10.8%)
Oedema peripheral	40/269 (14.9%)		31/268 (11.6%)
Pyrexia	47/269 (17.5%)		50/268 (18.7%)
Infections and infestations
Upper respiratory tract infection	13/269 (4.8%)		14/268 (5.2%)
Investigations
Alanine aminotransferase increased	19/269 (7.1%)		23/268 (8.6%)
Aspartate aminotransferase increased	17/269 (6.3%)		17/268 (6.3%)
Neutrophil count decreased	60/269 (22.3%)		58/268 (21.6%)
Weight decreased	20/269 (7.4%)		15/268 (5.6%)
White blood cell count decreased	55/269 (20.4%)		57/268 (21.3%)
Metabolism and nutrition disorders
Decreased appetite	98/269 (36.4%)		68/268 (25.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	15/269 (5.6%)		18/268 (6.7%)
Back pain	24/269 (8.9%)		21/268 (7.8%)
Muscle Spasms	14/269 (5.2%)		7/268 (2.6%)
Muscular Weakness	14/269 (5.2%)		9/268 (3.4%)
Musculoskeletal chest pain	19/269 (7.1%)		24/268 (9%)
Musculoskeletal pain	22/269 (8.2%)		14/268 (5.2%)
Myalgia	28/269 (10.4%)		26/268 (9.7%)
Pain in extremity	13/269 (4.8%)		14/268 (5.2%)
Nervous system disorders
Dizziness	14/269 (5.2%)		19/268 (7.1%)
Dysgeusia	25/269 (9.3%)		16/268 (6%)
Headache	35/269 (13%)		21/268 (7.8%)
Paraesthesia	21/269 (7.8%)		6/268 (2.2%)
Peripheral sensory neuropathy	44/269 (16.4%)		24/268 (9%)
Psychiatric disorders
Insomnia	16/269 (5.9%)		20/268 (7.5%)
Respiratory, thoracic and mediastinal disorders
Cough	42/269 (15.6%)		42/268 (15.7%)
Dyspnoea	57/269 (21.2%)		52/268 (19.4%)
Haemoptysis	19/269 (7.1%)		20/268 (7.5%)
Productive cough	16/269 (5.9%)		14/268 (5.2%)
Skin and subcutaneous tissue disorders
Alopecia	81/269 (30.1%)		42/268 (15.7%)
Rash	17/269 (6.3%)		24/268 (9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.