Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT02178241
• Collaborator: (none)
• Enrollment: 26
• Locations: 18
• Arm: 1
• Actual Duration (Months): 55
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies how well gemcitabine hydrochloride and eribulin mesylate work in treating patients with bladder cancer that has spread to other places in the body or cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride and eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Ureter Carcinoma; Metastatic Urethral Carcinoma; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7; Stage III Ureter Cancer AJCC v7; Stage III Urethral Cancer AJCC v7; Stage IV Bladder Urothelial Carcinoma AJCC v7; Stage IV Ureter Cancer AJCC v7; Stage IV Urethral Cancer AJCC v7; Ureter Urothelial Carcinoma; Urethral Urothelial Carcinoma	Drug: Eribulin Mesylate; Drug: Gemcitabine Hydrochloride	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To estimate the objective response rate of gemcitabine (gemcitabine hydrochloride)-eribulin (eribulin mesylate) (GE) when given to cisplatin ineligible patients with advanced or unresectable urothelial carcinoma who have not received any prior chemotherapy for the advanced disease.

SECONDARY OBJECTIVES:

1. To estimate the median progression-free survival (PFS). II. To summarize the toxicity profile (using Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4 criteria) of the GE regimen in these patients.

OUTLINE:

Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8 and eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 36 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Gemcitabine-Eribulin (GE) in Cisplatin Ineligible Patients With Advanced or Unresectable Urothelial Carcinoma of the Bladder
• Actual Study Start Date: Dec 11, 2014
• Actual Primary Completion Date: Mar 18, 2019
• Actual Study Completion Date: Jul 11, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (eribulin mesylate and gemcitabine hydrochloride) Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: Eribulin Mesylate; Given IV; Other Names: B1939 Mesylate E7389 ER-086526 Halaven Halichondrin B Analog ; Drug: Gemcitabine Hydrochloride; Given IV; Other Names: dFdCyd Difluorodeoxycytidine Hydrochloride FF 10832 FF-10832 FF10832 Gemcitabine HCI Gemzar LY-188011 LY188011

Outcome Measures

Primary Outcome Measures

1. Observed Overall Response Rate [Up to 36 months]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Observed Overall Response Rate = Number of patients who experienced a confirmed CR or PR divided by the number of eligible patients who began treatment.

Secondary Outcome Measures

1. Progression-free Survival [From the start until progression, death, or the start of another treatment, assessed up to 12 months]

   Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

2. Overall Survival [From start of treatment until death from any cause ,up to 36 months]

   Estimated using the product-limit method of Kaplan and Meier.

3. Incidence of Adverse Events. [Up to 36 months]

   Toxicities that Occurred in 10% or More of Patients or At Least Once as a Grade 3+ Adverse Event (excluding those toxicities classified as "unrelated" or "unlikely related" to study drugs). Toxicities graded using CTCAEv4 criteria.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have locally advanced or metastatic predominantly urothelial carcinoma of the bladder, ureter, or urethra that is not amenable to curative surgical treatment

• Patients must have histologically confirmed predominantly urothelial carcinoma of the bladder, ureter, or urethra

• Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam

• Patients must be ineligible for treatment with cisplatin, based on one of:

• Calculated creatinine clearance (CrCl) >= 30 and < 60 mL/min (Cockcroft-Gault)

• CTCAE grade (Gr) >= 2 hearing loss

• CTCAE Gr >= 2 neuropathy

• Patients must not have received prior systemic therapy for their advanced cancer; prior intravesical therapy completed 4 weeks prior to enrollment and adjuvant/neoadjuvant chemotherapy completed more than 6 months prior to diagnosis of advanced disease are permitted

• Zubrod performance status =< 2 (Karnofsky >= 60%)

• Life expectancy of greater than 3 months

• Leukocytes >= 3,000/mcL

• Absolute neutrophil count >= 1,500/mcL

• Platelets >= 100,000/mcL

• Total bilirubin < 1.5 times the upper limit of normal (x ULN) for the institution

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal

• Creatinine clearance; calculated creatinine clearance (CrCl) >= 30 mL/min and < 60 mL/min (Cockroft-Gault) unless the patient qualified based on hearing loss or neuropathy

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of gemcitabine and eribulin administration

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients with a small cell component in their histology are excluded

• Patients who have had chemotherapy for the treatment of the advanced or unresectable urothelial cancer of the bladder are not eligible; patients who were previously treated for local disease must not have received radiotherapy or chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study and must have recovered from adverse events due to agents administered more than 4 weeks earlier; patients who have received neoadjuvant or adjuvant chemotherapy must have completed treatment at least 6 months prior to diagnosis of metastatic disease

• Patients who are receiving any other investigational agents

• Patients with known brain metastases should be excluded from this clinical trial

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine and eribulin

• Uncontrolled intercurrent illness including, but not limited to, a second cancer diagnosis within the past 5 years, or a cancer undergoing any treatment, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with eribulin and gemcitabine

• Human immunodeficiency virus (HIV)-positive patients with inadequate cluster of differentiation (CD)4 counts or those who are on combination antiretroviral therapy with strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) effects are ineligible for this trial

• Patients with baseline corrected QT (QTc) prolongation greater than grade 1 are excluded from this study; patients with grade 1 QTc elevation are eligible but must be monitored with electrocardiogram (ECG) (EKG) exams, for the first 3 cycles of treatment; eribulin time to maximum concentration (Cmax) after infusion is about 10 minutes, and half life is 40 minutes; ECG (EKG) should be performed between 10 to 40 minutes after eribulin administration (on day 1 and day 8 of treatment); continued ECG (EKG) monitoring beyond cycle 3 can be done at the discretion of the treating physician

• Patients with congenital long QT syndrome are excluded from this study

• Other medications known to prolong QT interval should be discontinued and if not possible, patient is excluded from this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
2	Los Angeles County-USC Medical Center	Los Angeles	California	United States	90033
3	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
4	Keck Medical Center of USC Pasadena	Pasadena	California	United States	91105
5	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
6	University of Colorado Hospital	Aurora	Colorado	United States	80045
7	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
8	Moffitt Cancer Center P2C	Tampa	Florida	United States	33612
9	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
10	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois	United States	60451
11	Mayo Clinic Cancer Center P2C	Rochester	Minnesota	United States	55905
12	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
13	Case Western Reserve University	Cleveland	Ohio	United States	44106
14	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
15	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
16	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania	United States	15232
17	University of Texas M D Anderson Cancer Center P2C	Houston	Texas	United States	77030
18	University Health Network Princess Margaret Cancer Center P2C	Toronto	Ontario	Canada	M5G 2M9

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Sarmad Sadeghi, City of Hope Comprehensive Cancer Center LAO

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 20, 2017

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02178241
• Other Study ID Numbers: NCI-2014-01294; NCI-2014-01294; P9653_A02PAMDREVW01; PHII-130; 9653; 9653; N01CM00038; P30CA093373
• First Posted: Jun 30, 2014
• Last Update Posted: Dec 16, 2019
• Last Verified: Nov 1, 2019

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Transitional Cell; Urethral Neoplasms; Ureteral Neoplasms; Gemcitabine; Halichondrin B

Study Results

Participant Flow

Recruitment Details	Twenty-six patients were enrolled, but 2 did not receive treatment due to medication compliance related to diabetes and another deemed ineligible after registration but prior to treatment start.

Arm/Group Title	Treatment (Eribulin Mesylate and Gemcitabine Hydrochloride)
Arm/Group Description	Patients receive 1000mg/m^2 gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and 1.4mg/m^2 eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Eribulin Mesylate: Given IV Gemcitabine Hydrochloride: Given IV
Period Title: Overall Study
STARTED	24
COMPLETED	24
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Eribulin Mesylate and Gemcitabine Hydrochloride)
Arm/Group Description	Patients receive 1000mg/m^2 gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and 1.4mg/m^2 eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Eribulin Mesylate: Given IV Gemcitabine Hydrochloride: Given IV
Overall Participants	24
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	73
Sex: Female, Male (Count of Participants)
Female	4 16.7%
Male	20 83.3%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	22 91.7%
Hispanic	1 4.2%
Asian	1 4.2%
Region of Enrollment (participants) [Number]
United States	24 100%

Outcome Measures

1. Primary Outcome

Title	Observed Overall Response Rate
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Observed Overall Response Rate = Number of patients who experienced a confirmed CR or PR divided by the number of eligible patients who began treatment.
Time Frame	Up to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Eribulin Mesylate and Gemcitabine Hydrochloride)
Arm/Group Description	Patients receive 1000mg/m^2 gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and 1.4mg/m^2 eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Eribulin Mesylate: Given IV Gemcitabine Hydrochloride: Given IV
Measure Participants	24
Number (95% Confidence Interval) [percentage of participants]	50 208.3%

2. Secondary Outcome

Title	Progression-free Survival
Description	Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	From the start until progression, death, or the start of another treatment, assessed up to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Eribulin Mesylate and Gemcitabine Hydrochloride)
Arm/Group Description	Patients receive 1000mg/m^2 gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and 1.4mg/m^2 eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Eribulin Mesylate: Given IV Gemcitabine Hydrochloride: Given IV
Measure Participants	24
Median (95% Confidence Interval) [months]	5.3

3. Secondary Outcome

Title	Overall Survival
Description	Estimated using the product-limit method of Kaplan and Meier.
Time Frame	From start of treatment until death from any cause ,up to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Eribulin Mesylate and Gemcitabine Hydrochloride)
Arm/Group Description	Patients receive 1000mg/m^2 gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and 1.4mg/m^2 eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Eribulin Mesylate: Given IV Gemcitabine Hydrochloride: Given IV
Measure Participants	24
Median (95% Confidence Interval) [months]	11.9

4. Secondary Outcome

Title	Incidence of Adverse Events.
Description	Toxicities that Occurred in 10% or More of Patients or At Least Once as a Grade 3+ Adverse Event (excluding those toxicities classified as "unrelated" or "unlikely related" to study drugs). Toxicities graded using CTCAEv4 criteria.
Time Frame	Up to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Eribulin Mesylate and Gemcitabine Hydrochloride)
Arm/Group Description	Patients receive 1000mg/m^2 gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and 1.4mg/m^2 eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Eribulin Mesylate: Given IV Gemcitabine Hydrochloride: Given IV
Measure Participants	24
Grade 1 or 2 : Anemia	7 29.2%
Grade 1 or 2 : Febrile neutropenia	3 12.5%
Grade 1 or 2 : Thrombotic microangiopathy	1 4.2%
Grade 1 or 2 : Chest pain - cardiac	0 0%
Grade 1 or 2 : Heart failure	0 0%
Grade 1 or 2 : Colitis	0 0%
Grade 1 or 2 : Constipation	10 41.7%
Grade 1 or 2 : Diarrhea	7 29.2%
Grade 1 or 2 : Dry Mouth	4 16.7%
Grade 1 or 2 : Mucositis oral	2 8.3%
Grade 1 or 2 : Nausea	7 29.2%
Grade 1 or 2 : Vomiting	2 8.3%
Grade 1 or 2 : Edema	9 37.5%
Grade 1 or 2 : Fatigue	13 54.2%
Grade 1 or 2 : Fever	4 16.7%
Grade 1 or 2 : Appendicitis perforated	0 0%
Grade 1 or 2 : Lung infection	0 0%
Grade 1 or 2 : Sepsis	0 0%
Grade 1 or 2 : Upper respiratory infection	0 0%
Grade 1 or 2 : Urinary Tract Infection	1 4.2%
Grade 1 or 2 : Electrocardiogram QT	2 8.3%
Grade 1 or 2 : Weight Loss	4 16.7%
Grade 1 or 2 : Lymphocyte Count Decreased	4 16.7%
Grade 1 or 2 : Neutrophil Count Decreased	4 16.7%
Grade 1 or 2 : Platelet Count Decreased	7 29.2%
Grade 1 or 2 : White Blood Cell Decreased	7 29.2%
Grade 1 or 2 : INR increased	1 4.2%
Grade 1 or 2 : Alanine Aminotransferase Increased	9 37.5%
Grade 1 or 2 : Aspartate Aminotransferase Incr	11 45.8%
Grade 1 or 2 : Creatinine Increased	4 16.7%
Grade 1 or 2 : Anorexia	9 37.5%
Grade 1 or 2 : Hyperglycemia	0 0%
Grade 1 or 2 : Dehydration	3 12.5%
Grade 1 or 2 : Hypoalbuminemia	8 33.3%
Grade 1 or 2 : Hypocalcemia	4 16.7%
Grade 1 or 2 : Hypokalemia	4 16.7%
Grade 1 or 2 : Hypomagnesemia	3 12.5%
Grade 1 or 2 : Hyponatremia	7 29.2%
Grade 1 or 2 : Hypophosphatemia	4 16.7%
Grade 1 or 2 : Generalized Muscle Weakness	5 20.8%
Grade 1 or 2 : Grip Weakness	0 0%
Grade 1 or 2 : Pain in Extremity	3 12.5%
Grade 1 or 2 : Dizziness	5 20.8%
Grade 1 or 2 : Dysgeusia	4 16.7%
Grade 1 or 2 : Paresthesia	4 16.7%
Grade 1 or 2 : Peripheral Sensory Neuropathy	5 20.8%
Grade 1 or 2 : Insomnia	3 12.5%
Grade 1 or 2 : Dyspnea	0 0%
Grade 1 or 2 : Pneumonitis	0 0%
Grade 1 or 2 : Sore Throat	3 12.5%
Grade 1 or 2 : Alopecia	12 50%
Grade 1 or 2 : Hypotension	2 8.3%
Grade 1 or 2 : Thromboembolic event	0 0%
Grade 3 or 4 : Anemia	8 33.3%
Grade 3 or 4 : Febrile neutropenia	0 0%
Grade 3 or 4 : Thrombotic microangiopathy	0 0%
Grade 3 or 4 : Chest pain - cardiac	1 4.2%
Grade 3 or 4 : Heart failure	1 4.2%
Grade 3 or 4 : Colitis	1 4.2%
Grade 3 or 4 : Constipation	0 0%
Grade 3 or 4 : Diarrhea	2 8.3%
Grade 3 or 4 : Dry Mouth	0 0%
Grade 3 or 4 : Mucositis oral	2 8.3%
Grade 3 or 4 : Nausea	3 12.5%
Grade 3 or 4 : Vomiting	2 8.3%
Grade 3 or 4 : Edema	1 4.2%
Grade 3 or 4 : Fatigue	7 29.2%
Grade 3 or 4 : Fever	0 0%
Grade 3 or 4 : Appendicitis perforated	1 4.2%
Grade 3 or 4 : Lung infection	1 4.2%
Grade 3 or 4 : Sepsis	1 4.2%
Grade 3 or 4 : Upper respiratory infection	1 4.2%
Grade 3 or 4 : Urinary Tract Infection	2 8.3%
Grade 3 or 4 : Electrocardiogram QT	1 4.2%
Grade 3 or 4 : Weight Loss	0 0%
Grade 3 or 4 : Lymphocyte Count Decreased	6 25%
Grade 3 or 4 : Neutrophil Count Decreased	15 62.5%
Grade 3 or 4 : Platelet Count Decreased	3 12.5%
Grade 3 or 4 : White Blood Cell Decreased	13 54.2%
Grade 3 or 4 : INR increased	1 4.2%
Grade 3 or 4 : Alanine Aminotransferase Increased	0 0%
Grade 3 or 4 : Aspartate Aminotransferase Incr	1 4.2%
Grade 3 or 4 : Creatinine Increased	0 0%
Grade 3 or 4 : Anorexia	0 0%
Grade 3 or 4 : Hyperglycemia	1 4.2%
Grade 3 or 4 : Dehydration	2 8.3%
Grade 3 or 4 : Hypoalbuminemia	1 4.2%
Grade 3 or 4 : Hypocalcemia	0 0%
Grade 3 or 4 : Hypokalemia	0 0%
Grade 3 or 4 : Hypomagnesemia	0 0%
Grade 3 or 4 : Hyponatremia	2 8.3%
Grade 3 or 4 : Hypophosphatemia	0 0%
Grade 3 or 4 : Generalized Muscle Weakness	1 4.2%
Grade 3 or 4 : Grip Weakness	1 4.2%
Grade 3 or 4 : Pain in Extremity	1 4.2%
Grade 3 or 4 : Dizziness	0 0%
Grade 3 or 4 : Dysgeusia	0 0%
Grade 3 or 4 : Paresthesia	1 4.2%
Grade 3 or 4 : Peripheral Sensory Neuropathy	0 0%
Grade 3 or 4 : Insomnia	0 0%
Grade 3 or 4 : Dyspnea	1 4.2%
Grade 3 or 4 : Pneumonitis	1 4.2%
Grade 3 or 4 : Sore Throat	0 0%
Grade 3 or 4 : Alopecia	0 0%
Grade 3 or 4 : Hypotension	1 4.2%
Grade 3 or 4 : Thromboembolic event	1 4.2%

Adverse Events

Time Frame	Adverse events occurred over a period of 2 years and 10 months.
Adverse Event Reporting Description	"Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Arm/Group Title	Treatment (Eribulin Mesylate and Gemcitabine Hydrochloride)
Arm/Group Description	Patients receive 1000mg/m^2 gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and 1.4mg/m^2 eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Eribulin Mesylate: Given IV Gemcitabine Hydrochloride: Given IV
All Cause Mortality
	Treatment (Eribulin Mesylate and Gemcitabine Hydrochloride)
	Affected / at Risk (%)	# Events
Total	20/24 (83.3%)
Serious Adverse Events
	Treatment (Eribulin Mesylate and Gemcitabine Hydrochloride)
	Affected / at Risk (%)	# Events
Total	16/24 (66.7%)
Blood and lymphatic system disorders
Anemia	1/24 (4.2%)	2
Febrile neutropenia	2/24 (8.3%)	2
Thrombotic Microangiopathy	1/24 (4.2%)	1
Cardiac disorders
Atrial fibrillation	1/24 (4.2%)	1
Chest pain - cardiac	1/24 (4.2%)	1
Heart failure	2/24 (8.3%)	2
Myocardial infarction	1/24 (4.2%)	1
Gastrointestinal disorders
Colitis	3/24 (12.5%)	3
Nausea	2/24 (8.3%)	3
Vomiting	2/24 (8.3%)	2
General disorders
Death NOS	1/24 (4.2%)	1
Edema limbs	1/24 (4.2%)	1
Fatigue	2/24 (8.3%)	2
Fever	1/24 (4.2%)	1
Infections and infestations
Appendicitis perforated	1/24 (4.2%)	1
CELLULITIS	1/24 (4.2%)	1
Lung infection	1/24 (4.2%)	1
Sepsis	3/24 (12.5%)	3
Upper respiratory infection	1/24 (4.2%)	1
Urinary tract	1/24 (4.2%)	1
Urinary tract infection	3/24 (12.5%)	4
Injury, poisoning and procedural complications
Fall	1/24 (4.2%)	1
Investigations
Neutrophil count decreased	2/24 (8.3%)	3
White blood cell decreased	4/24 (16.7%)	7
Metabolism and nutrition disorders
Dehydration	3/24 (12.5%)	4
Hyperglycemia	1/24 (4.2%)	1
Hypoalbuminemia	1/24 (4.2%)	1
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	2/24 (8.3%)	2
Pain in extremity	1/24 (4.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death	1/24 (4.2%)	1
Disease progression	1/24 (4.2%)	1
Nervous system disorders
Dizziness	2/24 (8.3%)	2
Renal and urinary disorders
Acute kidney injury	2/24 (8.3%)	2
Urinary tract obstruction	1/24 (4.2%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/24 (8.3%)	2
Pneumonitis	2/24 (8.3%)	2
Vascular disorders
Hypotension	2/24 (8.3%)	2
Thromboembolic event	2/24 (8.3%)	2
Other (Not Including Serious) Adverse Events
	Treatment (Eribulin Mesylate and Gemcitabine Hydrochloride)
	Affected / at Risk (%)	# Events
Total	24/24 (100%)
Blood and lymphatic system disorders
Anemia	18/24 (75%)	113
Febrile neutropenia	1/24 (4.2%)	1
Cardiac disorders
Atrial fibrillation	1/24 (4.2%)	1
Chest Pain	1/24 (4.2%)	1
Heart failure	1/24 (4.2%)	1
Sinus tachycardia	1/24 (4.2%)	1
Endocrine disorders
Hyperthyroidism	1/24 (4.2%)	5
Eye disorders
Blurred vision	2/24 (8.3%)	5
Cataract	1/24 (4.2%)	6
Dry eye	2/24 (8.3%)	6
Watering eyes	2/24 (8.3%)	3
Gastrointestinal disorders
Abdominal distension	1/24 (4.2%)	1
Abdominal pain	5/24 (20.8%)	5
Bloating	1/24 (4.2%)	1
Constipation	13/24 (54.2%)	42
DUODENITIS	1/24 (4.2%)	1
Diarrhea	11/24 (45.8%)	16
Dry mouth	4/24 (16.7%)	16
Dysphagia	3/24 (12.5%)	5
Flatulence	1/24 (4.2%)	12
Gum Bleeding	1/24 (4.2%)	2
Heartburn	1/24 (4.2%)	2
Hemorrhoids	1/24 (4.2%)	13
Mucositis oral	4/24 (16.7%)	5
Nausea	11/24 (45.8%)	19
Rectal fistula	1/24 (4.2%)	1
Toothache	1/24 (4.2%)	2
Vomiting	6/24 (25%)	8
hematochiza	1/24 (4.2%)	1
General disorders
Chills	2/24 (8.3%)	2
Edema limbs	11/24 (45.8%)	46
Fatigue	20/24 (83.3%)	117
Fever	8/24 (33.3%)	16
Flu like symptoms	1/24 (4.2%)	1
Gait disturbance	1/24 (4.2%)	1
Infusion related reaction	2/24 (8.3%)	2
Injection site reaction	2/24 (8.3%)	2
Leg Pain	1/24 (4.2%)	1
Localized edema	1/24 (4.2%)	1
Malaise	2/24 (8.3%)	2
Non-cardiac chest pain	2/24 (8.3%)	2
Pain	7/24 (29.2%)	25
Plantar fasciitis	1/24 (4.2%)	1
injection site reaction	1/24 (4.2%)	1
vein irritation	1/24 (4.2%)	1
Infections and infestations
Athlete's foot	1/24 (4.2%)	2
Lung infection	1/24 (4.2%)	2
Pharyngitis	1/24 (4.2%)	2
Skin infection	3/24 (12.5%)	6
Toe infection	1/24 (4.2%)	1
Upper respiratory infection	3/24 (12.5%)	5
Urinary tract infection	10/24 (41.7%)	18
oral thrush	1/24 (4.2%)	1
Injury, poisoning and procedural complications
Bruising	4/24 (16.7%)	12
Fall	1/24 (4.2%)	1
Fracture	1/24 (4.2%)	1
Investigations
Activated partial thromboplastin time pr	1/24 (4.2%)	8
Alanine aminotransferase increased	13/24 (54.2%)	33
Alkaline phosphatase increased	6/24 (25%)	16
Aspartate aminotransferase increased	12/24 (50%)	42
Blood bilirubin increased	2/24 (8.3%)	5
Cardiac troponin I increased	1/24 (4.2%)	5
Creatinine increased	10/24 (41.7%)	34
Decreased ANC	1/24 (4.2%)	2
Decreased Creatinine Clearance	1/24 (4.2%)	1
Electrocardiogram QT corrected interval	3/24 (12.5%)	8
INR increased	4/24 (16.7%)	21
Lactic Acidosis Increased	1/24 (4.2%)	1
Lymphocyte count decreased	10/24 (41.7%)	67
Neutrophil count decreased	18/24 (75%)	72
Platelet count decreased	10/24 (41.7%)	49
Weight loss	4/24 (16.7%)	14
White blood cell decreased	18/24 (75%)	107
Metabolism and nutrition disorders
Acidosis	1/24 (4.2%)	1
Anorexia	10/24 (41.7%)	30
Decreased eGFR	1/24 (4.2%)	4
Dehydration	3/24 (12.5%)	3
Hypercalcemia	1/24 (4.2%)	1
Hyperglycemia	9/24 (37.5%)	35
Hyperkalemia	3/24 (12.5%)	6
Hypermagnesemia	1/24 (4.2%)	2
Hypoalbuminemia	13/24 (54.2%)	65
Hypocalcemia	11/24 (45.8%)	31
Hypoglycemia	1/24 (4.2%)	4
Hypokalemia	8/24 (33.3%)	9
Hypomagnesemia	4/24 (16.7%)	15
Hyponatremia	10/24 (41.7%)	20
Hypophosphatemia	9/24 (37.5%)	27
elevated LDH	1/24 (4.2%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	2/24 (8.3%)	5
Back pain	3/24 (12.5%)	4
Generalized muscle weakness	6/24 (25%)	22
Grip Weakness	1/24 (4.2%)	14
Muscle spasms	1/24 (4.2%)	1
Muscle weakness lower limb	1/24 (4.2%)	1
Myalgia	1/24 (4.2%)	1
Pain in extremity	5/24 (20.8%)	12
grip weakness	1/24 (4.2%)	2
Nervous system disorders
Amnesia	1/24 (4.2%)	2
Dizziness	5/24 (20.8%)	25
Dysgeusia	4/24 (16.7%)	10
Lethargy	1/24 (4.2%)	1
Paresthesia	6/24 (25%)	41
Peripheral motor neuropathy	3/24 (12.5%)	10
Peripheral sensory neuropathy	8/24 (33.3%)	28
Psychiatric disorders
Anxiety	2/24 (8.3%)	3
Confusion	2/24 (8.3%)	2
Depression	3/24 (12.5%)	8
Insomnia	5/24 (20.8%)	10
Suicidal ideation	1/24 (4.2%)	1
Renal and urinary disorders
Dysuria	1/24 (4.2%)	1
Hematuria	7/24 (29.2%)	13
Proteinuria	1/24 (4.2%)	1
Urinary frequency	1/24 (4.2%)	3
Respiratory, thoracic and mediastinal disorders
Chest Congestion	1/24 (4.2%)	1
Cough	5/24 (20.8%)	11
Dyspnea	5/24 (20.8%)	15
Hemoptysis	1/24 (4.2%)	1
Hoarseness	1/24 (4.2%)	10
Hypoxia	1/24 (4.2%)	1
Nasal congestion	4/24 (16.7%)	5
Productive cough	2/24 (8.3%)	3
Shortness of Breath	1/24 (4.2%)	1
Sore throat	4/24 (16.7%)	7
Skin and subcutaneous tissue disorders
Alopecia	13/24 (54.2%)	76
Erythema	1/24 (4.2%)	2
Erythema RT Lower Leg	1/24 (4.2%)	1
Erythema- RT Lower Leg	1/24 (4.2%)	1
IV site discomfort	1/24 (4.2%)	1
Pruritus	2/24 (8.3%)	6
Purple Macular Lesion Back of Neck	1/24 (4.2%)	1
Purple Macular Lesion Base of Neck	1/24 (4.2%)	4
Purple Macular Leson Base of Neck	1/24 (4.2%)	1
Rash acneiform	1/24 (4.2%)	1
increased nail growth	1/24 (4.2%)	2
Surgical and medical procedures
Mediport Placement	1/24 (4.2%)	1
Right Cataract Surgery	1/24 (4.2%)	2
Vascular disorders
Hypertension	7/24 (29.2%)	27
Hypotension	3/24 (12.5%)	9
Superficial thrombophlebitis	1/24 (4.2%)	1
Thromboembolic event	1/24 (4.2%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.