Clinical trial NCT00337077: Eribulin Mesylate in Treating Patients With Metastatic Prostate Cancer That Did Not Respond to Hormone Therapy
Official title: A Phase II Trial of E7389 (Halichondrin B Analog), in Patients With Metastatic Hormone Refractory Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adenocarcinoma of the Prostate
Hormone-refractory Prostate Cancer
Recurrent Prostate Cancer
Stage IV Prostate Cancer
Keywords: Eribulin Mesylate
metastatic hormone refractory prostate cancer
Halichondrin B Analog
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-06-15
Enrollment: 121
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial is studying how well eribulin mesylate (E7389; Halichondrin B Analog) works in treating patients with metastatic prostate cancer that did not respond to hormone therapy. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Detailed description: PRIMARY OBJECTIVES:

I. Determine the number of patients with a \> 50% decrease in prostate-specific antigen (PSA) of at least 4 weeks duration in patients with hormone-refractory metastatic prostate cancer treated with E7389 (eribulin mesylate).

SECONDARY OBJECTIVES:

I. Estimate the measurable disease response in patients with measurable disease.

II. Determine the duration of PSA and measurable disease response.

III. Characterize the safety and tolerability of E7389 in these patients.

OUTLINE:

This study enrolled 3 cohorts of patients based on the number of prior chemotherapy regimens received. The 3 cohorts are chemonaive stratum, prior-taxane stratum, and two-prior-chemotherapy stratum. Patients receive eribulin mesylate intravenously (IV) over 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 periodically for 5 years.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed adenocarcinoma of the prostate
* Progressive metastatic disease or stable metastatic disease with rising PSA
* Previously treated with bilateral orchiectomy or other primary hormonal therapy with evidence of treatment failure
* Patients who have not undergone bilateral orchiectomy must continue luteinizing hormone-releasing hormone (LHRH)-agonist therapy (e.g., leuprolide or goserelin) or LHRH antagonist therapy (e.g. abarelix) while receiving study treatment
* Patients who did not have an orchiectomy must have a testosterone level \< 50 ng/dL to confirm androgen suppression within the past 4 weeks
* ECOG performance status 0-2
* Adequate bone marrow function
* Bilirubin =\< 1.5 mg/dL
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 times upper limit of normal
* Creatinine =\< 2.0 mg/dL OR creatinine clearance \>= 40 mL/min
* Fertile patients must use effective contraception
* A taxane-based regimen, mitoxantrone, or other cytotoxic chemotherapy regimen allowed provided there is evidence of disease progression
* At least 4 weeks since prior chemotherapy or radiotherapy
* At least 4 weeks since prior flutamide (6 weeks for bicalutamide or nilutamide) and there is continued evidence of disease progression
* Disease progression after antiandrogen withdrawal must be confirmed by rising PSA after the required 4-6 week washout period (e.g., PSA level higher than the last PSA obtained while on antiandrogen therapy)
* More than 4 weeks since prior estrogen, estrogen-like agents (e.g., PC-SPES, saw palmetto, or other herbal products that may contain phytoestrogens), or any other hormonal therapy (including megestrol, finasteride, ketoconazole, or systemic corticosteroids)
* Concurrent bisphosphonates (e.g., pamidronate sodium or zoledronate) allowed provided the patient has been receiving the bisphosphonate for \>= 4 weeks and there is evidence of disease progression

Exclusion Criteria:

* Active angina pectoris
* Known New York Heart Association class III-IV heart disease
* Myocardial infarction within the past 6 months
* Evidence of ventricular dysrhythmias or other unstable arrhythmia (rate-controlled atrial fibrillation is allowed if the patient is asymptomatic from a cardiac standpoint)
* Peripheral neuropathy \> grade 2
* Other prior malignancy (excluding nonmelanomatous skin cancer treated with curative intent) unless the malignancy was treated with curative intent and the patient has been disease free for \>= 5 years
* Serious concurrent medical illness or active infection that would preclude study treatment - No concurrent strong inhibitors or inducers of CYP3A4
* More than 2 prior chemotherapy regimens for hormone-refractory disease - Other concurrent investigational agents
* Other concurrent anticancer therapy, including chemotherapy, gene therapy, biologic therapy, or immunotherapy
* Concurrent palliative radiotherapy
* Concurrent estrogen, estrogen-like agents, or any other hormonal therapy
* Carcinomatous meningitis or brain metastases
* Prior strontium chloride Sr 89, samarium 153 lexidronam pentasodium, or other radioisotopes
* Concurrent therapeutic anticoagulation with warfarin (Unfractionated heparin \[standard, low-dose, or adjusted dose\] or low molecular weight heparin allowed

Primary outcomes:
measure: Proportion of Patients With PSA Response
timeFrame: Assessed every 3 weeks during treatment; after off-treatment, every 3 months if patient is <2 years from study entry and every 6 months if patient is 2-5 years
Secondary outcomes:
measure: Proportion of Patients With Measurable Disease Response
timeFrame: Assessed every 9 weeks during treatment; after off-treatment, every 3 months if patient is <2 years from study entry and every 6 months if patient is 2-5 years from study entry
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Monterey
country: United States
facility: Community Hospital of Monterey Peninsula
state: California
city: Manchester
country: United States
facility: Manchester Memorial Hospital
state: Connecticut
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Aurora
country: United States
facility: Rush - Copley Medical Center
state: Illinois
city: Bloomington
country: United States
facility: Saint Joseph Medical Center
state: Illinois
city: Canton
country: United States
facility: Graham Hospital Association
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Mercy Hospital and Medical Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Elgin
country: United States
facility: Sherman Hospital
state: Illinois
city: Eureka
country: United States
facility: Eureka Hospital
state: Illinois
city: Evanston
country: United States
facility: Evanston CCOP-NorthShore University HealthSystem
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Galesburg
country: United States
facility: Illinois CancerCare Galesburg
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Hopedale
country: United States
facility: Hopedale Medical Complex - Hospital
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates Limited
state: Illinois
city: Kewanee
country: United States
facility: Kewanee Hospital
state: Illinois
city: Macomb
country: United States
facility: Mcdonough District Hospital
state: Illinois
city: Moline
country: United States
facility: Garneau, Stewart C MD (UIA Investigator)
state: Illinois
city: Moline
country: United States
facility: Porubcin, Michael MD (UIA Investigator)
state: Illinois
city: Moline
country: United States
facility: Sharis, Christine M MD (UIA Investigator)
state: Illinois
city: Moline
country: United States
facility: Stoffel, Thomas J MD (UIA Investigator)
state: Illinois
city: Moline
country: United States
facility: Vigliotti, Antonio, P.G. M.D. (UIA Investigator)
state: Illinois
city: Normal
country: United States
facility: Bromenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center Foundation
state: Illinois
city: Ottawa
country: United States
facility: Illinois CancerCare-Ottawa Clinic
state: Illinois
city: Ottawa
country: United States
facility: Ottawa Regional Hospital and Healthcare Center
state: Illinois
city: Pekin
country: United States
facility: Pekin Cancer Treatment Center
state: Illinois
city: Pekin
country: United States
facility: Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Peoria
country: United States
facility: Illinois Oncology Research Association CCOP
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Hospital
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Skokie
country: United States
facility: Edward H Kaplan MD and Associates
state: Illinois
city: Spring Valley
country: United States
facility: Saint Margaret's Hospital
state: Illinois
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Clinic-Urbana Main
state: Illinois
city: Urbana
country: United States
facility: Carle Foundation - Carle Cancer Center
state: Illinois
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: Kokomo
country: United States
facility: Community Howard Regional Health
state: Indiana
city: La Porte
country: United States
facility: Indiana University Health La Porte Hospital
state: Indiana
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Center
state: Indiana
city: Mishawaka
country: United States
facility: Saint Joseph Regional Medical Center-Mishawaka
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic
state: Iowa
city: Bettendorf
country: United States
facility: Constantinou, Costas L MD (UIA Investigator)
state: Iowa
city: Cedar Rapids
country: United States
facility: Cedar Rapids Oncology Association
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Hospital
state: Iowa
city: Cedar Rapids
country: United States
facility: Oncology Associates at Mercy Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Capitol
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Iowa Oncology Research Association CCOP
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates
state: Iowa
city: Des Moines
country: United States
facility: Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Iowa Lutheran Hospital
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology Oncology Associates
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center-Sioux City
state: Iowa
city: Sioux City
country: United States
facility: Saint Luke's Regional Medical Center
state: Iowa
city: Boston
country: United States
facility: Eastern Cooperative Oncology Group
state: Massachusetts
city: Adrian
country: United States
facility: Bixby Medical Center
state: Michigan
city: Adrian
country: United States
facility: Hickman Cancer Center
state: Michigan
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Ann Arbor
country: United States
facility: Michigan Cancer Research Consortium Community Clinical Oncology Program
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Hospital
state: Michigan
city: Detroit
country: United States
facility: Saint John Hospital and Medical Center
state: Michigan
city: Escanaba
country: United States
facility: Green Bay Oncology - Escanaba
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Flint
country: United States
facility: Genesys Regional Medical Center-West Flint Campus
state: Michigan
city: Iron Mountain
country: United States
facility: Green Bay Oncology - Iron Mountain
state: Michigan
city: Jackson
country: United States
facility: Allegiance Health
state: Michigan
city: Lansing
country: United States
facility: Sparrow Hospital
state: Michigan
city: Livonia
country: United States
facility: Saint Mary Mercy Hospital
state: Michigan
city: Monroe
country: United States
facility: Community Cancer Center of Monroe
state: Michigan
city: Monroe
country: United States
facility: Mercy Memorial Hospital
state: Michigan
city: Pontiac
country: United States
facility: Saint Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Saint Joseph Mercy Port Huron
state: Michigan
city: Saginaw
country: United States
facility: Saint Mary's of Michigan
state: Michigan
city: St. Joseph
country: United States
facility: Lakeland Hospital
state: Michigan
city: Warren
country: United States
facility: Saint John Macomb-Oakland Hospital
state: Michigan
city: Bemidji
country: United States
facility: Sanford Clinic North-Bemidgi
state: Minnesota
city: Duluth
country: United States
facility: Essentia Health Duluth Clinic CCOP
state: Minnesota
city: Duluth
country: United States
facility: Essentia Health Saint Mary's Medical Center
state: Minnesota
city: Duluth
country: United States
facility: Miller-Dwan Hospital
state: Minnesota
city: Hutchinson
country: United States
facility: Hutchinson Area Health Care
state: Minnesota
city: Litchfield
country: United States
facility: Meeker County Memorial Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Saint John's Hospital - Healtheast
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: Saint Joseph's Hospital - Healtheast
state: Minnesota
city: Shakopee
country: United States
facility: Saint Francis Regional Medical Center
state: Minnesota
city: Woodbury
country: United States
facility: Woodwinds Health Campus
state: Minnesota
city: Flemington
country: United States
facility: Hunterdon Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical CCOP
state: New Jersey
city: Hamilton
country: United States
facility: Cancer Institute of New Jersey At Hamilton
state: New Jersey
city: Mount Holly
country: United States
facility: Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: Voorhees
country: United States
facility: Virtua West Jersey Hospital Voorhees
state: New Jersey
city: Bronx
country: United States
facility: The North Division of Montefiore Medical Center
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: Fargo
country: United States
facility: Sanford Clinic North-Fargo
state: North Dakota
city: Fargo
country: United States
facility: Sanford Medical Center-Fargo
state: North Dakota
city: Bowling Green
country: United States
facility: Toledo Clinic Cancer Centers-Bowling Green
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Clyde
country: United States
facility: North Coast Cancer Care-Clyde
state: Ohio
city: Elyria
country: United States
facility: Hematology Oncology Center Incorporated
state: Ohio
city: Lima
country: United States
facility: Lima Memorial Hospital
state: Ohio
city: Maumee
country: United States
facility: Toledo Clinic Cancer Centers-Maumee
state: Ohio
city: Maumee
country: United States
facility: Saint Luke's Hospital
state: Ohio
city: Maumee
country: United States
facility: Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
state: Ohio
city: Oregon
country: United States
facility: Saint Charles Hospital
state: Ohio
city: Oregon
country: United States
facility: Toledo Clinic Cancer Centers-Oregon
state: Ohio
city: Sandusky
country: United States
facility: North Coast Cancer Care
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital
state: Ohio
city: Tiffin
country: United States
facility: Mercy Hospital of Tiffin
state: Ohio
city: Toledo
country: United States
facility: The Toledo Hospital/Toledo Children's Hospital
state: Ohio
city: Toledo
country: United States
facility: Saint Vincent Mercy Medical Center
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Toledo
country: United States
facility: Toledo Community Hospital Oncology Program CCOP
state: Ohio
city: Toledo
country: United States
facility: Mercy Cancer Center at Saint Anne Mercy Hospital
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic Cancer Centers-Toledo
state: Ohio
city: Wauseon
country: United States
facility: Fulton County Health Center
state: Ohio
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Bethlehem
country: United States
facility: Saint Luke's Hospital
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Lewistown
country: United States
facility: Lewistown Hospital
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany Medical Center
state: Pennsylvania
city: Fredericksburg
country: United States
facility: Fredericksburg Oncology Inc
state: Virginia
city: Green Bay
country: United States
facility: Green Bay Oncology at Saint Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology Limited at Saint Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Mary's Hospital
state: Wisconsin
city: Madison
country: United States
facility: UW Health Oncology - 1 South Park
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Medical Center
state: Wisconsin
city: Oconto Falls
country: United States
facility: Green Bay Oncology - Oconto Falls
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology - Sturgeon Bay
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Riverview Hospital
state: Wisconsin
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Mark Stein, M.D.
role: STUDY_CHAIR
References:
citation: Stein MN, Chen Y, Hudes GR, Carducci MA, Tan W, DiPaola RS. ECOG 5805: A phase II study of eribulin mesylate (E7389) in patients (pts) with metastatic castration-resistant prostate cancer (CRPC). J Clin Oncol 28:15s, 2010 (suppl; abstr 4556)