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A Phase I/II Study of E7389 Halichondrin B Analog (NSC # 707389; IND # 64395) in Metastatic Urothelial Tract Cancer and Renal Insufficiency


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Distal Urethral Cancer, Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter, Proximal Urethral Cancer, Recurrent Bladder Cancer, Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter, Recurrent Urethral Cancer, Regional Transitional Cell Cancer of the Renal Pelvis and Ureter, Stage III Bladder Cancer, Stage IV Bladder Cancer, Transitional Cell Cancer of the Renal Pelvis and Ureter, Urethral Cancer, Urethral Cancer Associated With Invasive Bladder Cancer

Thank you

Trial Information

A Phase I/II Study of E7389 Halichondrin B Analog (NSC # 707389; IND # 64395) in Metastatic Urothelial Tract Cancer and Renal Insufficiency


PRIMARY OBJECTIVES:

I. To establish whether E7389 can be given safely to patients with moderate and severe renal
dysfunction at 1.4 mg/m2/week (the 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)

OUTLINE: This is a multicenter, dose-escalation, phase I study followed by an open-label
phase II study. Patients in the phase I portion of the study are stratified by renal
dysfunction (moderate vs severe).

PHASE I: Patients receive eribulin mesylate intravenously (IV) over 1-2 minutes on days 1
and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable
toxicity.

PHASE II: Patients receive eribulin mesylate IV over 1-2 minutes on days 1 and 8 at the MTD.
Treatment repeats every 21 days in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed periodically for at least 6
months.


Inclusion Criteria:



- Locally advanced or metastatic disease that is not amenable to surgical treatment

- No brain metastasis that is unstable (i.e., presenting with neurologic symptoms that
progress or require increasing doses of steroids within a 4-week period) or is
untreated (i.e., not radiated)

- Life expectancy > 6 months

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No uncontrolled intercurrent illness including, but not limited to, any of the
following: ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris, cardiac arrhythmia, psychiatric illness or social
situations that would limit study compliance

- No more than 2 prior lines of therapy (for patients enrolled in phase I); more than 6
months since prior chemotherapy in the adjuvant setting* [Note: *for patients
enrolled at dose level 3 of phase I and all of phase II]

- No other concurrent investigational agents

- No other concurrent anticancer agents or therapies

- No concurrent prophylactic granulocyte or platelet colony-stimulating factors

- Measurable disease, defined as >= 1 lesion that can be accurately measured in >= 1
dimension as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
(for patients enrolled in phase II or dose level 3 of phase I)

- Absolute neutrophil count >= 1,000/mm^3

- Platelet count >= 100,000/mm^3

- Hemoglobin >= 9 g/dL

- Bilirubin =< 1.5 times upper limit of normal (ULN)

- AST and ALT =< 2.5 times ULN

- Patients must have either (a) normal kidney function (i.e. creatinine =< 1.5 X 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

- Histologically or cytologically confirmed urothelial tract carcinoma

- ECOG performance status (PS) 0-2 or Karnofsky PS 70-100%

- No HIV-positive patients on combination antiretroviral therapy or with CD4+ count ≤
500/mm³

- No concurrent dialysis

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD and RP2D of eribulin mesylate graded according to CTCAE v4.0 (phase I)

Outcome Time Frame:

21 days

Safety Issue:

Yes

Principal Investigator

David Quinn

Investigator Role:

Principal Investigator

Investigator Affiliation:

City of Hope Medical Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00170

NCT ID:

NCT00365157

Start Date:

October 2006

Completion Date:

Related Keywords:

  • Distal Urethral Cancer
  • Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter
  • Proximal Urethral Cancer
  • Recurrent Bladder Cancer
  • Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter
  • Recurrent Urethral Cancer
  • Regional Transitional Cell Cancer of the Renal Pelvis and Ureter
  • Stage III Bladder Cancer
  • Stage IV Bladder Cancer
  • Transitional Cell Cancer of the Renal Pelvis and Ureter
  • Urethral Cancer
  • Urethral Cancer Associated With Invasive Bladder Cancer
  • Urinary Bladder Neoplasms
  • Renal Insufficiency
  • Urethral Neoplasms
  • Carcinoma, Transitional Cell
  • Kidney Neoplasms
  • Ureteral Neoplasms

Name

Location

University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
Loyola University Medical CenterMaywood, Illinois  60153
Medical College of WisconsinMilwaukee, Wisconsin  53226
Ingalls Memorial HospitalHarvey, Illinois  60426
City of Hope Comprehensive Cancer CenterDuarte, California  91010
Central Illinois Hematology Oncology CenterSpringfield, Illinois  62701
City of Hope Medical CenterDuarte, California  91010
City of HopeDuarte, California  91010
Contra Costa Regional Medical CenterMartinez, California  94553-3156
Tower Cancer Research FoundationBeverly Hills, California  90211
University of ChicagoChicago, Illinois  60637
USC Norris Comprehensive Cancer CenterLos Angeles, California  90089
UC Davis Comprehensive Cancer CenterSacramento, California  95817
Decatur Memorial HospitalDecatur, Illinois  62526
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
University of Southern CaliforniaLos Angeles, California  90033
Northern Indiana Cancer Research ConsortiumSouth Bend, Indiana  
Joliet Oncology-Hematology Associates LimitedJoliet, Illinois  60435
Illinois CancerCare-PeoriaPeoria, Illinois  61615
Fort Wayne Medical Oncology and Hematology Inc - State BoulevardFort Wayne, Indiana  46845
Saint John's Mercy Medical CenterSaint Louis, Missouri  63141
University of Maryland Greenebaum Cancer CenterBaltimore, Maryland  21201
Oncology Care Associates PLLCSt. Joseph, Michigan  49085
City of Hope Medical Group IncPasadena, California  91105
Community Howard Regional HealthKokomo, Indiana  46904
Veterans Administration Hospital - MartinezMartinez, California  94553
Kellogg Cancer Center - Evanston HospitalEvanston, Illinois  60201
Southern Illinois University School of Medicine - Department of SurgerySpringfield, Illinois  62702
UPMC Cancer Center - PittsburghPittsburgh, Pennsylvania  15241