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

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ClinicalTrials.gov Identifier: NCT02178241
Recruitment Status : Active, not recruiting
First Posted : June 30, 2014
Last Update Posted : March 15, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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:

I. 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:

I. 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
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 : December 11, 2014
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019


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
  • Gemzar
  • LY-188011
  • LY188011




Primary Outcome Measures :
  1. Objective response rate defined as either a confirmed complete response (CR) or a confirmed partial response (PR) based on RECIST version 1.1 [ Time Frame: Up to 36 months ]

Secondary Outcome Measures :
  1. PFS using RECIST v1.1 [ Time Frame: From the start of treatment on day 1, until progression, death, or the start of another treatment, assessed up to 12 months ]
    PFS will be summarized with a Kaplan-Meier plot and confidence intervals (at 3, 6, 9, and 12 months).

  2. Overall survival [ Time Frame: Up to 36 months ]
    Summarized with a Kaplan-Meier plot and confidence intervals.

  3. Incidence of adverse events as graded by the CTCAE v. 4 [ Time Frame: Up to 36 months ]
    All observed toxicities will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by the CTCAE v4.0), and time of onset (i.e. course of treatment). Tables will be created to summarize these toxicities and side effects, overall, by course - possibly by the cause of the cisplatin ineligibility, if numbers permit.

  4. Overall response rate (ORR) [ Time Frame: Up to 36 months ]
    ORR will be calculated as the ratio of the number of eligible patients who experienced a confirmed CR or PR (by RECIST v1.1) divided by the total number of eligible patients who began treatment; 90% confidence intervals will be constructed. A secondary estimate (more conservative) of the overall response rate will count in the numerator, only those patients who experienced a confirmed CR or PR AND who received 2 or more doses of eribulin mesylate.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02178241


Locations
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United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010
Los Angeles County-USC Medical Center
Los Angeles, California, United States, 90033
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Keck Medical Center of USC Pasadena
Pasadena, California, United States, 91105
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80045
United States, District of Columbia
MedStar Georgetown University Hospital
Washington, District of Columbia, United States, 20007
United States, Florida
Moffitt Cancer Center P2C
Tampa, Florida, United States, 33612
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, United States, 60451
United States, Minnesota
Mayo Clinic Cancer Center P2C
Rochester, Minnesota, United States, 55905
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
University of Texas M D Anderson Cancer Center P2C
Houston, Texas, United States, 77030
Canada, Ontario
University Health Network Princess Margaret Cancer Center P2C
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Sarmad Sadeghi City of Hope Comprehensive Cancer Center LAO

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02178241     History of Changes
Other Study ID Numbers: NCI-2014-01294
NCI-2014-01294 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P9653_A02PAMDREVW01
PHII-130
9653 ( Other Identifier: City of Hope Comprehensive Cancer Center LAO )
9653 ( Other Identifier: CTEP )
N01CM00038 ( U.S. NIH Grant/Contract )
P30CA093373 ( U.S. NIH Grant/Contract )
First Posted: June 30, 2014    Key Record Dates
Last Update Posted: March 15, 2019
Last Verified: March 2019

Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Transitional Cell
Urethral Neoplasms
Ureteral Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urethral Diseases
Urologic Diseases
Ureteral Diseases
Gemcitabine
Halichondrin B
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators