Eribulin Mesylate in Treating Patients With Metastatic Prostate Cancer That Did Not Respond to Hormone Therapy

Adenocarcinoma of the Prostate Clinical Trial

Official title:

A Phase II Trial of E7389 (Halichondrin B Analog), in Patients With Metastatic Hormone Refractory Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00337077
• Other study ID #: NCI-2009-00566
• Secondary ID: NCI-2009-00566E5
• Status: Completed
• Phase: Phase 2
• First received: June 13, 2006
• Last updated: May 21, 2014
• Start date: November 2006
• Est. completion date: November 2013

Study information

• Verified date: April 2014
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: November 2013
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Prostate
• Hormone-refractory Prostate Cancer
• Prostatic Neoplasms
• Recurrent Prostate Cancer
• Stage IV Prostate Cancer

Intervention

Drug:
• eribulin mesylate
Given IV

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center	Adrian	Michigan
United States	McFarland Clinic	Ames	Iowa
United States	Michigan Cancer Research Consortium Community Clinical Oncology Program	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Sanford Clinic North-Bemidgi	Bemidji	Minnesota
United States	Saint Luke's Hospital	Bethlehem	Pennsylvania
United States	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Eastern Cooperative Oncology Group	Boston	Massachusetts
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	The North Division of Montefiore Medical Center	Bronx	New York
United States	Graham Hospital Association	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cedar Rapids Oncology Association	Cedar Rapids	Iowa
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Mercy Hospital and Medical Center	Chicago	Illinois
United States	Case Western Reserve University	Cleveland	Ohio
United States	North Coast Cancer Care-Clyde	Clyde	Ohio
United States	Oakwood Hospital	Dearborn	Michigan
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa Oncology Research Association CCOP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Capitol	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Essentia Health Duluth Clinic CCOP	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Sherman Hospital	Elgin	Illinois
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Hematology Oncology Center Incorporated	Elyria	Ohio
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Eureka Hospital	Eureka	Illinois
United States	Evanston CCOP-NorthShore University HealthSystem	Evanston	Illinois
United States	Sanford Clinic North-Fargo	Fargo	North Dakota
United States	Sanford Medical Center-Fargo	Fargo	North Dakota
United States	Hunterdon Medical Center	Flemington	New Jersey
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Fredericksburg Oncology Inc	Fredericksburg	Virginia
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Illinois CancerCare Galesburg	Galesburg	Illinois
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital	Green Bay	Wisconsin
United States	Hackensack University Medical CCOP	Hackensack	New Jersey
United States	Cancer Institute of New Jersey At Hamilton	Hamilton	New Jersey
United States	Mason District Hospital	Havana	Illinois
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Hopedale Medical Complex - Hospital	Hopedale	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Allegiance Health	Jackson	Michigan
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Joliet Oncology-Hematology Associates Limited	Joliet	Illinois
United States	Kewanee Hospital	Kewanee	Illinois
United States	Community Howard Regional Health	Kokomo	Indiana
United States	Indiana University Health La Porte Hospital	La Porte	Indiana
United States	Sparrow Hospital	Lansing	Michigan
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Lima Memorial Hospital	Lima	Ohio
United States	Meeker County Memorial Hospital	Litchfield	Minnesota
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Mcdonough District Hospital	Macomb	Illinois
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	UW Health Oncology - 1 South Park	Madison	Wisconsin
United States	Manchester Memorial Hospital	Manchester	Connecticut
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Saint Luke's Hospital	Maumee	Ohio
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	Saint Anthony Memorial Health Center	Michigan City	Indiana
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
United States	Garneau, Stewart C MD (UIA Investigator)	Moline	Illinois
United States	Porubcin, Michael MD (UIA Investigator)	Moline	Illinois
United States	Sharis, Christine M MD (UIA Investigator)	Moline	Illinois
United States	Stoffel, Thomas J MD (UIA Investigator)	Moline	Illinois
United States	Vigliotti, Antonio, P.G. M.D. (UIA Investigator)	Moline	Illinois
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital	Monroe	Michigan
United States	Community Hospital of Monterey Peninsula	Monterey	California
United States	Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County	Mount Holly	New Jersey
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	New York University Langone Medical Center	New York	New York
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center Foundation	Normal	Illinois
United States	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin
United States	Saint Charles Hospital	Oregon	Ohio
United States	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Pekin Cancer Treatment Center	Pekin	Illinois
United States	Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois Oncology Research Association CCOP	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Saint Joseph Mercy Port Huron	Port Huron	Michigan
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Mayo Clinic	Rochester	Minnesota
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Regions Hospital	Saint Paul	Minnesota
United States	Saint Joseph's Hospital - Healtheast	Saint Paul	Minnesota
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Hematology Oncology Associates	Sioux City	Iowa
United States	Edward H Kaplan MD and Associates	Skokie	Illinois
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	Saint Margaret's Hospital	Spring Valley	Illinois
United States	Memorial Medical Center	Springfield	Illinois
United States	Lakeland Hospital	St. Joseph	Michigan
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Flower Hospital	Sylvania	Ohio
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Mercy Cancer Center at Saint Anne Mercy Hospital	Toledo	Ohio
United States	Saint Vincent Mercy Medical Center	Toledo	Ohio
United States	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	Carle Clinic-Urbana Main	Urbana	Illinois
United States	Carle Foundation - Carle Cancer Center	Urbana	Illinois
United States	Virtua West Jersey Hospital Voorhees	Voorhees	New Jersey
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Fulton County Health Center	Wauseon	Ohio
United States	Riverview Hospital	Wisconsin Rapids	Wisconsin
United States	Woodwinds Health Campus	Woodbury	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients With PSA Response	PSA response is defined as a PSA decline from baseline value by >=50%, or normalization of PSA (<0.2 ng/ml) confirmed by a second measurement greater than or equal to 4 weeks later.	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	No
Secondary	Proportion of Patients With Measurable Disease Response	Measurable disease response was evaluated using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria. Per RECIST criteria, complete response (CR) = disappearance of all target and non-target lesions. Partial response (PR)= >=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Measurable disease response = CR + PR. Only patients with measurable disease at baseline are included in this analysis.	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	No