Eribulin Mesylate in Treating Patients With Locally Advanced or Metastatic Cancer of the Urothelium and Kidney Dysfunction

NCT00365157 | Active Not Recruiting Phase 1 DMC

• 12 other identifiers: NCI-2009-00170CDR0000492014PHII-757435N01CM00038N01CM00071N01CM62201N01CM62209P30CA033572U01CA062505UM1CA186705UM1CA186717
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 26

Brief Summary

This phase I/II trial studies the effect of eribulin mesylate and to see how well it works in treating patients with cancer of the urothelium that has spread to nearby tissue (locally advanced) or to other places in the body (metastatic)and kidney dysfunction. Drugs used in chemotherapy, such as 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. Chemotherapy drugs may have different effects in patients who have changes in their kidney function.

Conditions

Advanced Urothelial Carcinoma; Locally Advanced Urothelial Carcinoma; Metastatic Urothelial Carcinoma; Recurrent Urothelial Carcinoma; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7; Stage IV Bladder Urothelial Carcinoma AJCC v7; Unresectable Urothelial Carcinoma

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of eribulin mesylate for patients who have received a tubulin-inhibitor for the recurrent/advanced disease (Phase I)

  MTD and RP2D will be graded according to Common Terminology Criteria for Adverse (CTCAE) version 5.0.

  21 days

• MTD and RP2D of eribulin mesylate for patients who have not received a tubulin-inhibitor for the recurrent/advanced disease (Phase I)

  MTD and RP2D will be graded according to CTCAE version 5.0.

  21 days

• Overall response rate

  Calculated as the ratio of the number of eligible patients who experienced a confirmed complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors version 1.1 (Phase II). 95% confidence intervals will be constructed.

  Up to 6 months

Secondary Outcomes (4)

• Progression-free survival (Phase II)

  From the start of treatment on day 1 until progression, death, or the start of another treatment, assessed at 6 months

• Progression-free survival (Phase II)

  From the start of treatment on day 1 until progression, death, or the start of another treatment, assessed up to 12 months

• Overall survival (Phase II)

  From the start of treatment on day 1 until progression, death, or the start of another treatment, assessed up to 12 months

• Incidence of adverse events

  Up to 24 months

Other Outcomes (3)

• Pharmacokinetic parameters for eribulin mesylate

  At baseline; at 5, 10, 15, and 30 minutes; and at 1, 2, 4, 6, 8, 12, and 24 hours on day 1 of course 1 and at end of days 2-4 and 8 of course 1

• Expression levels of the tubulin isotypes

  Baseline

• Disease control rate (complete response [CR] + partial response [PR] + stable disease [SD])

  12 weeks

Study Arms (1)

Treatment (eribulin mesylate)

EXPERIMENTAL

Patients receive eribulin mesylate IV over 1-2 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Eribulin Mesylate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Eribulin Mesylate DRUG

Given IV

Also known as: B1939 Mesylate, E7389, ER-086526 Mesylate, Halaven, Halichondrin B Analog

Treatment (eribulin mesylate)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (eribulin mesylate)

Pharmacological Study OTHER

Correlative studies

Treatment (eribulin mesylate)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have locally advanced or metastatic urothelial cancer that is not amenable to surgical treatment
• Patients must have histologically or cytologically confirmed urothelial tract carcinoma
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan
• All patients may have received up to two prior lines of chemotherapy for recurrent/advanced disease
• Patients must have received at least one platinum-based chemotherapy for recurrent/advanced disease; recurrent disease is defined as having recurred after definitive therapy and advanced disease is defined as T4 and/or N2 and/or M1; in addition, for completion of Cohort #2, patients must also have received a tubulin inhibitor as part of their therapy for urothelial cancer; for purposes of this evaluation, treatment with chemotherapy regimens where carboplatin or similar is substituted for cisplatin or where a taxane is added or removed will be considered the same regimen; tubulin inhibitors in common use include paclitaxel, docetaxel, and vinblastine; the exception to this requirement applies to women
• Women with and without prior therapy are also eligible; priority will be given to those who consent to participating in the pharmacokinetic studies
• Life expectancy of greater than 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and Karnofsky \>= 60%
• Absolute neutrophil count \>= 1,000/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dL
• Total bilirubin =\< 1.5 institutional upper limit of normal (IULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X IULN
• Patients must have either (a) normal kidney function (i.e. creatinine =\< 1.5 X upper limit of normal \[ULN\] OR calculated creatinine clearance \>= 60 mL/min by the modified Cockcroft and Gault Formula OR a creatinine clearance \>= 60 mL/min obtained from a 24-hour urine collection) or (b) moderate or severe renal dysfunction (i.e. creatinine clearance \< 60 mL/min and \>= 20 mL/min)
• Patients with symptomatic uremia, uncontrolled edema or unstable serum electrolytes should not enter the trial until such time as they have been stabilized - such patients should be discussed with the principal investigator

You may not qualify if:

• Patients may not be receiving any other investigational agents
• Patients with brain metastasis that are unstable (i.e. presenting with neurologic symptoms that progress or require increasing doses of steroids within a 4-week period) or are untreated (i.e. not radiated) should be excluded
• Uncontrolled intercurrent illness including, but not limited to, 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 because E7389 Halichondrin analog is tubulin inhibitor agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with E7389 Halichondrin analog, breastfeeding should be discontinued if the mother is treated with E7389
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with E7389 Halichondrin analog; HIV-positive patients with CD4+ =\< 500/mm3 are ineligible because they are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in this group of patients when indicated
• Prior therapy with E7389 Halichondrin analog (eribulin)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (26)

Tower Cancer Research Foundation

Beverly Hills, California, 90211, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

City of Hope Antelope Valley

Lancaster, California, 93534, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Contra Costa Regional Medical Center

Martinez, California, 94553-3156, United States

Location

Veterans Administration Hospital - Martinez

Martinez, California, 94553, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

Duly Health and Care Joliet

Joliet, Illinois, 60435, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

Location

Central Illinois Hematology Oncology Center

Springfield, Illinois, 62702, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

Location

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, 46845, United States

Location

Community Howard Regional Health

Kokomo, Indiana, 46904, United States

Location

Northern Indiana Cancer Research Consortium

South Bend, Indiana, 46628, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Oncology Care Associates PLLC

Saint Joseph, Michigan, 49085, United States

Location

Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

eribulin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• David I Quinn

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2006
• First Posted: August 17, 2006
• Study Start: October 23, 2006
• Primary Completion: July 9, 2025
• Study Completion (Estimated): July 9, 2026
• Last Updated: July 11, 2025

Record last verified: 2025-07

Locations

US (26)