Overview

This trial is active, not recruiting.

Conditions metastatic urothelial carcinoma, recurrent urothelial carcinoma of the renal pelvis and ureter, stage iii bladder cancer, stage iii urethral cancer, stage iv bladder cancer, stage iv urethral cancer
Treatments eribulin mesylate, laboratory biomarker analysis, pharmacological study
Phase phase 1/phase 2
Sponsor National Cancer Institute (NCI)
Start date October 2006
End date December 2016
Trial size 132 participants
Trial identifier NCT00365157, 7435, CDR0000492014, N01CM00038, N01CM00071, N01CM62201, N01CM62209, NCI-2009-00170, P30CA033572, PHII-75, U01CA062505, UM1CA186705

Summary

This phase I/II trial studies the side effects and best dose of eribulin mesylate and to see how well it works in treating patients with cancer of the urothelium that has spread to nearby tissue or to other places in the body 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive eribulin mesylate IV over 1-2 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
eribulin mesylate B1939 Mesylate
Given IV
laboratory biomarker analysis
Correlative studies
pharmacological study
Correlative studies

Primary Outcomes

Measure
MTD and recommended phase II dose (RP2D) of eribulin mesylate for patients who have received a tubulin-inhibitor for the recurrent/advanced disease, graded according to CTCAE v4.0 (Phase I)
time frame: 21 days
MTD and RP2D of eribulin mesylate for patients who have not received a tubulin-inhibitor for the recurrent/advanced disease, graded according to CTCAE v4.0 (Phase I)
time frame: 21 days
Overall response rate calculated as the ratio of the number of eligible patients who experienced a confirmed CR or PR by Response Evaluation Criteria in Solid Tumors v1.1 (Phase II)
time frame: Up to 6 months

Secondary Outcomes

Measure
Incidence of adverse events, graded according to the CTCAE v4.0
time frame: Up to 24 months
Overall survival (Phase II)
time frame: From the start of treatment on day 1 until progression, death, or the start of another treatment, assessed up to 12 months
Progression-free survival (Phase II)
time frame: 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)
time frame: From the start of treatment on day 1 until progression, death, or the start of another treatment, assessed up to 12 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - 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 - 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 - 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 Exclusion Criteria: - 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; breastfeeding should be discontinued if the mother is treated with E7389 - Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; HIV-positive patients with cluster of differentiation (CD)4+ =< 500/mm^3 are ineligible; appropriate studies will be undertaken in this group of patients when indicated - Prior therapy with E7389 Halichondrin analog (eribulin)

Additional Information

Official title A Phase I/II Study of E7389 Halichondrin B Analog (NSC # 707389) in Metastatic Urothelial Tract Cancer and Renal Insufficiency
Principal investigator David Quinn
Description PRIMARY OBJECTIVES: I. To establish whether E7389 (eribulin mesylate) 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 naïve. (Tubulin inhibitors in common use for urothelial cancer include paclitaxel, docetaxel and vinblastine). (Phase II) 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) 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) 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) 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) XI. To compare men and women with advanced bladder cancer treated with E7389 with respect to pharmacokinetics of E7389. (Enrollment to additional females) 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) OUTLINE: This is a phase I, dose-escalation study followed by a phase II study. Patients receive eribulin mesylate intravenously (IV) over 1-2 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 monthly for 12 months and then every 3 months for up to 24 months.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).
Location data was received from the National Cancer Institute and was last updated in November 2016.