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

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

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Prostate Cancer; Adenocarcinoma of the Prostate; Stage IV Prostate Cancer; Hormone-refractory Prostate Cancer
• Intervention / Treatment: Drug: eribulin mesylate

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.

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • California
    • Monterey, California, United States, 93940
      • Community Hospital of Monterey Peninsula
  • Connecticut
    • Manchester, Connecticut, United States, 06040
      • Manchester Memorial Hospital
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush - Copley Medical Center
    • Bloomington, Illinois, United States, 61701
      • Saint Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Graham Hospital Association
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Chicago, Illinois, United States, 60616
      • Mercy Hospital and Medical Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Elgin, Illinois, United States, 60123
      • Sherman Hospital
    • Eureka, Illinois, United States, 61530
      • Eureka Hospital
    • Evanston, Illinois, United States, 60201
      • Evanston CCOP-NorthShore University HealthSystem
    • Galesburg, Illinois, United States, 61401
      • Galesburg Cottage Hospital
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare Galesburg
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Hopedale, Illinois, United States, 61747
      • Hopedale Medical Complex - Hospital
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates Limited
    • Kewanee, Illinois, United States, 61443
      • Kewanee Hospital
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Moline, Illinois, United States, 61265
      • Garneau, Stewart C MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Porubcin, Michael MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Sharis, Christine M MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Stoffel, Thomas J MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Vigliotti, Antonio, P.G. M.D. (UIA Investigator)
    • Normal, Illinois, United States, 61761
      • Community Cancer Center Foundation
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Ottawa, Illinois, United States, 61350
      • Ottawa Regional Hospital and Healthcare Center
    • Pekin, Illinois, United States, 61554
      • Pekin Cancer Treatment Center
    • Pekin, Illinois, United States, 61554
      • Pekin Hospital
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peoria, Illinois, United States, 61603
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61615
      • Illinois Oncology Research Association CCOP
    • Peru, Illinois, United States, 61354
      • Illinois Valley Hospital
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Skokie, Illinois, United States, 60076
      • Edward H Kaplan MD and Associates
    • Spring Valley, Illinois, United States, 61362
      • Saint Margaret's Hospital
    • Springfield, Illinois, United States, 62781-0001
      • Memorial Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Clinic-Urbana Main
    • Urbana, Illinois, United States, 61801
      • Carle Foundation - Carle Cancer Center
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Kokomo, Indiana, United States, 46904
      • Community Howard Regional Health
    • La Porte, Indiana, United States, 46350
      • Indiana University Health La Porte Hospital
    • Michigan City, Indiana, United States, 46360
      • Saint Anthony Memorial Health Center
    • Mishawaka, Indiana, United States, 46545-1470
      • Saint Joseph Regional Medical Center-Mishawaka
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • Northern Indiana Cancer Research Consortium
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic
    • Bettendorf, Iowa, United States, 52722
      • Constantinou, Costas L MD (UIA Investigator)
    • Cedar Rapids, Iowa, United States, 52403
      • Mercy Hospital
    • Cedar Rapids, Iowa, United States, 52403
      • Oncology Associates at Mercy Medical Center
    • Cedar Rapids, Iowa, United States, 52403
      • Cedar Rapids Oncology Association
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50307
      • Mercy Capitol
    • Des Moines, Iowa, United States, 50309
      • Iowa Oncology Research Association CCOP
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates
    • Sioux City, Iowa, United States, 51104
      • Saint Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology Oncology Associates
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center-Sioux City
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Eastern Cooperative Oncology Group
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Bixby Medical Center
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium Community Clinical Oncology Program
    • Dearborn, Michigan, United States, 48124
      • Oakwood Hospital
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • Escanaba, Michigan, United States, 49431
      • Green Bay Oncology - Escanaba
    • Flint, Michigan, United States, 48502
      • Hurley Medical Center
    • Flint, Michigan, United States, 48532
      • Genesys Regional Medical Center-West Flint Campus
    • Iron Mountain, Michigan, United States, 49801
      • Green Bay Oncology - Iron Mountain
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital
    • Monroe, Michigan, United States, 48162
      • Community Cancer Center of Monroe
    • Pontiac, Michigan, United States, 48341-2985
      • Saint Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Saint Joseph Mercy Port Huron
    • Saginaw, Michigan, United States, 48601
      • Saint Mary's of Michigan
    • St. Joseph, Michigan, United States, 49085
      • Lakeland Hospital
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
  • Minnesota
    • Bemidji, Minnesota, United States, 56601
      • Sanford Clinic North-Bemidgi
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Saint Mary's Medical Center
    • Duluth, Minnesota, United States, 55805
      • Miller-Dwan Hospital
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Duluth Clinic CCOP
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Litchfield, Minnesota, United States, 55355
      • Meeker County Memorial Hospital
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • Saint Joseph's Hospital - Healtheast
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Woodbury, Minnesota, United States, 55125
      • Woodwinds Health Campus
  • New Jersey
    • Flemington, New Jersey, United States, 08822
      • Hunterdon Medical Center
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical CCOP
    • Hamilton, New Jersey, United States, 08690
      • Cancer Institute of New Jersey at Hamilton
    • Mount Holly, New Jersey, United States, 08060
      • Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
    • New Brunswick, New Jersey, United States, 08903
      • Cancer Institute of New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Virtua West Jersey Hospital Voorhees
  • New York
    • Bronx, New York, United States, 10466
      • The North Division of Montefiore Medical Center
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Sanford Clinic North-Fargo
    • Fargo, North Dakota, United States, 58122
      • Sanford Medical Center-Fargo
  • Ohio
    • Bowling Green, Ohio, United States, 43402
      • Toledo Clinic Cancer Centers-Bowling Green
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Clyde, Ohio, United States, 43410
      • North Coast Cancer Care-Clyde
    • Elyria, Ohio, United States, 44035
      • Hematology Oncology Center Incorporated
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Maumee, Ohio, United States, 43537
      • Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
    • Maumee, Ohio, United States, 43537
      • Saint Luke's Hospital
    • Maumee, Ohio, United States, 43537-1839
      • Toledo Clinic Cancer Centers-Maumee
    • Oregon, Ohio, United States, 43616
      • Saint Charles Hospital
    • Oregon, Ohio, United States, 43616
      • Toledo Clinic Cancer Centers-Oregon
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital
    • Tiffin, Ohio, United States, 44883
      • Mercy Hospital of Tiffin
    • Toledo, Ohio, United States, 43608
      • Saint Vincent Mercy Medical Center
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic Cancer Centers-Toledo
    • Toledo, Ohio, United States, 43614
      • University of Toledo
    • Toledo, Ohio, United States, 43617
      • Toledo Community Hospital Oncology Program CCOP
    • Toledo, Ohio, United States, 43606
      • The Toledo Hospital/Toledo Children's Hospital
    • Toledo, Ohio, United States, 43623
      • Mercy Cancer Center at Saint Anne Mercy Hospital
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Bethlehem, Pennsylvania, United States, 18015
      • Saint Luke's Hospital
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Milton S Hershey Medical Center
    • Lewistown, Pennsylvania, United States, 17044
      • Lewistown Hospital
    • State College, Pennsylvania, United States, 16803
      • Mount Nittany Medical Center
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology Inc
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology Limited at Saint Mary's Hospital
    • Green Bay, Wisconsin, United States, 54303
      • Saint Mary's Hospital
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology at Saint Vincent Hospital
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Madison, Wisconsin, United States, 53715
      • UW Health Oncology - 1 South Park
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • Oconto Falls, Wisconsin, United States, 54154
      • Green Bay Oncology - Oconto Falls
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology - Sturgeon Bay
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Riverview Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eribulin mesylate; Patients receive eribulin mesylate IV over 5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: eribulin mesylate; Given IV; Other Names: E7389; ER-086526; B1939; halichrondrin B analog

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Study Chair: Mark Stein, M.D., Rutgers Cancer Institute of New Jersey

Publications and helpful links

General Publications

• 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)

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: June 13, 2006
• First Submitted That Met QC Criteria: June 13, 2006
• First Posted (Estimate): June 15, 2006

Study Record Updates

• Last Update Posted (Estimate): June 23, 2014
• Last Update Submitted That Met QC Criteria: May 21, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Eribulin Mesylate; metastatic hormone refractory prostate cancer; Halichondrin B Analog
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: NCI-2009-00566 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA021115 (U.S. NIH Grant/Contract); E5805 (Other Identifier: Eastern Cooperative Oncology Group (ECOG))