Advanced Urothelial CarcinomaPhase 1/2NCT00365157
Eribulin Mesylate in Treating Patients With Locally Advanced or Metastatic Cancer of the Urothelium and Kidney Dysfunction
A Phase 1/2 study testing Eribulin Mesylate, Laboratory Biomarker Analysis and Pharmacological Study in people with Advanced Urothelial Carcinoma and Locally Advanced Urothelial Carcinoma, run by National Cancer Institute (NCI) at 26 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma
- What is being tested?
- Eribulin Mesylate, Laboratory Biomarker Analysis and Pharmacological Study
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 171 participants
- Where
- 26 sitesUnited States
- Study dates
- 23 Oct 2006to 9 Jul 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of E7389 Halichondrin analog will be determined following review of their case by the principal investigator
- The effects of E7389 Halichondrin analog on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because tubulin inhibitors are known to be teratogenic, women and men of child-bearing potential 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 participating in this study, she should inform her treating physician immediately
- Patients must have the ability to understand and the willingness to sign a written informed consent document
Who cannot join
- 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)
Trial locations and contacts
26 sites in 1 country.
26 sites in 1 country
United States26 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Tower Cancer Research Foundation
Beverly Hills, California, 90211
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Decatur Memorial Hospital
Decatur, Illinois, 62526
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201
Fort Wayne Medical Oncology and Hematology Inc-Parkview
Fort Wayne, Indiana, 46845
Ingalls Memorial Hospital
Harvey, Illinois, 60426
Duly Health and Care Joliet
Joliet, Illinois, 60435
Community Howard Regional Health
Kokomo, Indiana, 46904
City of Hope Antelope Valley
Lancaster, California, 93534
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Contra Costa Regional Medical Center
Martinez, California, 94553-3156
Veterans Administration Hospital - Martinez
Martinez, California, 94553
Loyola University Medical Center
Maywood, Illinois, 60153
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Oncology Care Associates PLLC
Saint Joseph, Michigan, 49085
Northern Indiana Cancer Research Consortium
South Bend, Indiana, 46628
City of Hope South Pasadena
South Pasadena, California, 91030
Central Illinois Hematology Oncology Center
Springfield, Illinois, 62702
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
About this study
Official title: A Phase I/II Study of E7389 Halichondrin B Analog (NSC # 707389) in Metastatic Urothelial Tract Cancer and Renal Insufficiency
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To establish whether eribulin mesylate (E7389) can be given safely to patients with moderate and severe renal dysfunction at 1.4 mg/m^2/week (the maximum tolerated dose [MTD] previously defined for patients with normal renal function) on days 1 and 8 of a 21-day cycle. (Phase I) II. To characterize the pharmacokinetic (PK) profile of E7389 in patients with moderate and severe renal dysfunction. (Phase I) III. To determine the response rate of patients with advanced urothelial carcinomas to E7389 in the first-line setting. (Phase II) IV. To determine the 6-month, progression-free survival and overall survival of patients with advanced urothelial carcinomas treated with E7389. (Phase II) V. To document the toxicity associated with the administration of E7389 to patients with advanced urothelial carcinoma patients and varying degrees of renal dysfunction. (Phase II) VI. To determine the response rate of patients with advanced urothelial carcinomas to E7389 in the setting of progression after prior platinum-based chemotherapy for advanced or recurrent disease, in two cohorts: tubulin-inhibitor treated or tubulin-inhibitor naive. (tubulin inhibitors in common use for urothelial cancer include paclitaxel, docetaxel and vinblastine). (Phase II) (per Amendment 6) VII. To determine the 6-month progression-free survival and overall survival of patients with advanced urothelial carcinomas treated with E7389 after platinum-based therapy for recurrent or advanced disease. (Phase II) (per Amendment 6) VIII. To document the toxicity associated with the administration of E7389 to patients with advanced urothelial carcinoma patients in the second line and later setting. (Phase II) (per Amendment 6) IX. To compare men and women with advanced bladder cancer treated with E7389 with respect to toxicity of E7389 as classified by Common Terminology Criteria for Adverse Events (CTCAE) version (v)4 for (i) all hematologic toxicities, (ii) all non- hematologic toxicities, and (iii) the most frequently observed toxicities (neutropenia, anemia, leucopenia, infection). (Enrollment to additional females) (per Amendment 11) X. To compare men and women with advanced bladder cancer treated with E7389 with respect to response to E7389 as evidenced by (i) disease control rate (DCR) defined as stable disease (SD)+partial response (PR)+complete response (CR) at 12 weeks, (ii) progression-free survival (PFS), and (iii) overall survival (OS). (Enrollment to additional females) (per Amendment 11) XI. To compare men and women with advanced bladder cancer treated with E7389 with respect to pharmacokinetics of E7389. (Enrollment to additional females) (per Amendment 11) XII. To compare men and women with advanced bladder cancer treated with E7389 with respect to tumoral expression of genes involved in the mechanism of action of E7389, including tubulin isotypes, microtubule-associated protein 4 (MAP4), and stathmin. (Enrollment to additional females) (per Amendment 11)
OUTLINE:
Patients receive eribulin mesylate intravenously (IV) over 1-2 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up monthly for 12 months and then every 3 months for up to 24 months.
- 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
- Being tested
- Eribulin Mesylate, Laboratory Biomarker Analysis, Pharmacological Study
- Medical subject headings
- Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eribulin MesylateDrug
Also called B1939 Mesylate, E7389, ER-086526 Mesylate, Halaven
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Eribulin Mesylate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Eribulin Mesylate for Patients Who Have Received a Tubulin-inhibitor for the Recurrent/Advanced Disease (Phase I)
MTD will be graded according to Common Terminology Criteria for Adverse (CTCAE) version 5.0.
Measured: 21 days
MTD of Eribulin Mesylate for Patients Who Have Not Received a Tubulin-inhibitor for the Recurrent/Advanced Disease (Phase I)
MTD will be graded according to CTCAE version 5.0.
Measured: 21 days
Number of Subjects With Overall Response
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1): Complete Response (CR), Disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter (LD) of target lesions; Overall Response (OR) = CR + PR
Measured: Up to 6 months
Secondary outcomes (4)
Progression-free Survival (Phase II)
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.1), as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, and appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Measured: 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)
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.1), as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, and appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Measured: 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)
Overall survival will be summarized as time from the start of treatment until death from any cause.
Measured: From the start of treatment on day 1 until death, assessed up to 12 months
Number of Participants With Adverse Events (AE)
Graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. All observed toxicities (excluding unrelated or unlikely related AEs) will be summarized from the start of treatment until the end of treatment visit up to 24 months, or until the patient dies or refuses further follow up.
Measured: Up to 24 months, or until the patient dies or refuses further follow up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2006 (estimated)
- Study start23 Oct 2006
- Primary completion9 Jul 2025
- Study completion9 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 171 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- David I Quinn, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00365157
- Sponsor's protocol ID
- NCI-2009-00170
- Other IDs
- NCI-2009-00170, CDR0000492014, PHII-75, 7435, 7435, N01CM00038, N01CM00071, N01CM62201
- Status last verified
- Aug 2026
- First submitted
- 16 Aug 2006
- Last updated
- 9 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes