Eribulin Mesylate in Treating Patients With Recurrent or Refractory Osteosarcoma

A Phase II Study of Eribulin (NSC# 707389) in Recurrent or Refractory Osteosarcoma

This phase II trial studies how well eribulin mesylate works in treating patients with osteosarcoma that has come back after treatment (recurrent) or has not responded to treatment (refractory). Microtubule inhibitors, such as eribulin mesylate, may stop or slow the growth of tumor cells by disrupting the cell cycle.

Study Overview

• Status: Completed
• Conditions: Recurrent Osteosarcoma
• Intervention / Treatment: Other: Pharmacological Study; Drug: Eribulin Mesylate

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the 4 month progression free survival rate and objective response rate in patients with recurrent osteosarcoma who are administered eribulin (eribulin mesylate) therapy on day 1 and day 8 of 21 day cycles.

SECONDARY OBJECTIVES:

I. To investigate the pharmacokinetics (PK) of eribulin in subjects with recurrent osteosarcoma.

II. To further describe the tolerability of single agent eribulin.

OUTLINE:

Patients receive eribulin mesylate intravenously (IV) over 2-5 minutes on days 1 and 8. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up annually for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • British Columbia Children's Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's Hospital of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Childrens Hospital
  • California
    • Downey, California, United States, 90242
      • Southern California Permanente Medical Group
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Los Angeles, California, United States, 90095
      • Mattel Children's Hospital UCLA
    • Madera, California, United States, 93636-8762
      • Children's Hospital Central California
    • Oakland, California, United States, 94611
      • Kaiser Permanente-Oakland
    • Oakland, California, United States, 94609-1809
      • Children's Hospital and Research Center at Oakland
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital Stanford University
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Alfred I duPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic-Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Orlando, Florida, United States, 32827
      • Nemours Children's Hospital
    • Pensacola, Florida, United States, 32504
      • Nemours Children's Clinic - Pensacola
    • Saint Petersburg, Florida, United States, 33701
      • All Children's Hospital
    • Tampa, Florida, United States, 33607
      • Saint Joseph's Hospital/Children's Hospital-Tampa
    • West Palm Beach, Florida, United States, 33407
      • Saint Mary's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta - Egleston
    • Savannah, Georgia, United States, 31404
      • Memorial University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital-Chicago
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Children's Hospital-Oak Lawn
    • Peoria, Illinois, United States, 61637
      • Saint Jude Midwest Affiliate
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
    • Indianapolis, Indiana, United States, 46260
      • Saint Vincent Hospital and Health Care Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky/Markey Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center Jefferson
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Children's Cancer Program
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • East Lansing, Michigan, United States, 48824-7016
      • Michigan State University Clinical Center
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Cancer Center
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minnesota - Minneapolis
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center-Fairview
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center-Carrie J Babb Cancer Center
    • Branson, Missouri, United States, 65616
      • CoxHealth Cancer Center
    • Joplin, Missouri, United States, 64804
      • Freeman Health System
    • Joplin, Missouri, United States, 64804
      • Mercy Hospital-Joplin
    • Kansas City, Missouri, United States, 64108
      • The Childrens Mercy Hospital
    • Rolla, Missouri, United States, 65401
      • Phelps County Regional Medical Center
    • Rolla, Missouri, United States, 65401
      • Saint John's Clinic-Rolla-Cancer and Hematology
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Saint Louis, Missouri, United States, 63109
      • Saint Louis Cancer and Breast Institute-South City
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68114
      • Children's Hospital and Medical Center of Omaha
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Comprehensive Cancer Centers of Nevada - Henderson
    • Henderson, Nevada, United States, 89052
      • Cancer and Blood Specialists-Henderson
    • Henderson, Nevada, United States, 89052
      • Las Vegas Cancer Center-Henderson
    • Henderson, Nevada, United States, 89074
      • Comprehensive Cancer Centers of Nevada-Southeast Henderson
    • Henderson, Nevada, United States, 89074
      • 21st Century Oncology - Henderson
    • Las Vegas, Nevada, United States, 89144
      • Summerlin Hospital Medical Center
    • Las Vegas, Nevada, United States, 89106
      • Radiation Oncology Centers of Nevada Central
    • Las Vegas, Nevada, United States, 89119
      • Radiation Oncology Centers of Nevada Southeast
    • Las Vegas, Nevada, United States, 89128
      • Comprehensive Cancer Centers of Nevada - Northwest
    • Las Vegas, Nevada, United States, 89144
      • Comprehensive Cancer Centers of Nevada-Summerlin
    • Las Vegas, Nevada, United States, 89148
      • Comprehensive Cancer Centers of Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada - Central Valley
    • Las Vegas, Nevada, United States, 89106
      • Cancer and Blood Specialists-Shadow
    • Las Vegas, Nevada, United States, 89109
      • HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
    • Las Vegas, Nevada, United States, 89113
      • HealthCare Partners Medical Group Oncology/Hematology-San Martin
    • Las Vegas, Nevada, United States, 89121
      • Cancer Therapy and Integrative Medicine
    • Las Vegas, Nevada, United States, 89128
      • Cancer and Blood Specialists-Tenaya
    • Las Vegas, Nevada, United States, 89128
      • HealthCare Partners Medical Group Oncology/Hematology-Tenaya
    • Las Vegas, Nevada, United States, 89148-2405
      • Las Vegas Cancer Center-Medical Center
    • Las Vegas, Nevada, United States, 89149
      • HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
    • Las Vegas, Nevada, United States, 89109
      • 21st Century Oncology
    • Las Vegas, Nevada, United States, 89148
      • Cancer and Blood Specialists-Fort Apache
    • Las Vegas, Nevada, United States, 89106
      • Nevada Cancer Research Foundation CCOP
    • Las Vegas, Nevada, United States, 89148
      • 21st Century Oncology - Fort Apache
    • Las Vegas, Nevada, United States, 89182
      • 21st Century Oncology - Vegas Tenaya
    • Las Vegas, Nevada, United States, 89109
      • Children's Specialty Center of Nevada II
  • New York
    • Bronx, New York, United States, 10467-2490
      • Montefiore Medical Center - Moses Campus
    • New Hyde Park, New York, United States, 11040
      • The Steven and Alexandra Cohen Children's Medical Center of New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital-Memorial Campus
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Sanford Medical Center-Fargo
  • Ohio
    • Akron, Ohio, United States, 44308
      • Children's Hospital Medical Center of Akron
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies and Childrens Hospital
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
    • Toledo, Ohio, United States, 43606
      • The Toledo Hospital/Toledo Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Children's Hospital
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Lehigh Valley Hospital - Muhlenberg
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Palmetto Health Richland
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117-5134
      • Sanford USD Medical Center - Sioux Falls
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • East Tennessee Childrens Hospital
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78207
      • Children's Hospital of San Antonio
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Childrens Hospital-King's Daughters
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
    • Spokane, Washington, United States, 99204
      • Providence Sacred Heart Medical Center and Children's Hospital
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 49 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have had histologic verification of osteosarcoma at original diagnosis
• Patients must have measurable disease, documented by clinical, radiographic, or histologic criteria, and have relapsed or become refractory to conventional therapy
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
• Patients must have a life expectancy of >= 8 weeks

• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study

  • Myelosuppressive chemotherapy: must not have received within 2 weeks of entry onto this study (6 weeks if prior nitrosourea)
  • Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent
  • Bisphosphonates: at least 4 weeks since the completion of therapy with a bisphosphonate
  • Monoclonal antibodies: at least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
  • Radiation therapy (RT): >= 2 weeks (wks) for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation
• Peripheral absolute neutrophil count (ANC) >= 1000/uL
• Platelet count >= 75,000/uL (transfusion independent)
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or

• A serum creatinine based on age/gender as follows: (threshold creatinine values were derived from the Schwartz formula for estimating GFR)

  • Age (12 to < 13 years) - serum creatinine of 1.2 mg/dL
  • Age (13 to < 16 years) - serum creatinine of 1.5 mg/dL (male) and 1.4 mg/dL (female)
  • Age (>= 16 years) - serum creatinine of 1.7 mg/dL (male) and 1.4 mg/dL (female)
• Bilirubin (sum of conjugate + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 units per liter (U/L); for the purpose of this study, the ULN for SGPT is 45 U/L
• Serum albumin > 2 g/dL
• Shortening fraction of >= 27% by echocardiogram
• Ejection fraction of >= 50% by radionuclide angiogram
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

• Patients with congenital prolonged QT syndrome
• Patients with a baseline QT/corrected QT (QTc) interval >= 501 msec
• Patients who are receiving drugs that prolong the QTc are not eligible
• Patients who have previously received eribulin, halichondrin B, or analogues of halichondrin B
• Patients who have grade >= 2 peripheral neuropathy
• Patients who are receiving other cancer directed therapy at the time of enrollment
• Patients who have had major surgery within 3 weeks prior to enrollment are not eligible; procedures such as placement of a central vascular catheter, or limited tumor biopsy, are not considered major surgery

• Pregnancy and breast feeding

  • Female patients who are pregnant are ineligible
  • Lactating females are not eligible unless they have agreed not to breastfeed their infants
  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
  • Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment (eribulin mesylate); Patients receive eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.	Other: Pharmacological Study; Correlative studies; Drug: Eribulin Mesylate; Given IV; Other Names: Halaven; E7389; ER-086526; Halichondrin B Analog

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Success	The number of patients who do not experience disease progression or death in the four months following enrollment on AOST1322.	4 Months
Response Evaluation Criteria in Solid Tumors (RECIST) Response	The number of patients who experience a complete or partial response according to the RECIST criteria as defined in Eisenhauer et al. Eur J Cancer 45:228-47, 2009.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Cycles Where a Dose Limiting Toxicity Was Identified	Each cycle where the patient receives eribulin and does not receive non-protocol anticancer therapy will be considered in the analysis. A dose limiting toxicity is defined to be: day 8 eribulin dose is held due to grade 3 or grade 4 non-hematological toxicity attributable to the investigational drug and does not resolve to meet eligibility or baseline criteria by day 11. Any >= grade 3 non-hematological toxicity attributable to the investigational drug with the specific exclusion of: grade 3 nausea and vomiting < 3 days duration grade 3 liver enzyme elevation, including alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/gamma-glutamyltransferase (GGT), that returns to grade =< 1 or baseline prior to the time for the next treatment cycle.	4 months
Area Under the Curve 0-infinity of Eribulin Mesylate in Ng-hr/ml	Data from all patients who provide samples for pharmacokinetic analysis will be aggregated. The sample mean and variance of the area under the curve will be reported The analytic unit will be the patient-cycle: Each cycle where the patient receives eribulin and does not receive non-protocol anticancer therapy will be considered in the analysis.	Cycle 1 day 1 and cycle 2 day 1 at the end of infusion, 0.5-6 hours, and 24-120 hours post infusion; cycle 1 day 8 and cycle 2 day 8 prior to the dose of eribulin and at the end of infusion
Clearance of Eribulin Mesylate in L/hr	Data from all patients who provide samples for pharmacokinetic analysis will be aggregated. The sample mean and variance of the clearance will be reported. The analytic unit will be the patient-cycle: Each cycle where the patient receives eribulin and does not receive non-protocol anticancer therapy will be considered in the analysis.	Cycle 1 day 1 and cycle 2 day 1 at the end of infusion, 0.5-6 hours, and 24-120 hours post infusion; cycle 1 day 8 and cycle 2 day 8 prior to the dose of eribulin and at the end of infusion.
A Half Life of Eribulin Mesylate in hr	Data from all patients who provide samples for pharmacokinetic analysis will be aggregated. The sample mean and variance of the half life will be reported. The analytic unit will be the patient-cycle: Each cycle where the patient receives eribulin and does not receive non-protocol anticancer therapy will be considered in the analysis.	1 day 1 and cycle 2 day 1 at the end of infusion, 0.5-6 hours, and 24-120 hours post infusion; cycle 1 day 8 and cycle 2 day 8 prior to the dose of eribulin and at the end of infusion

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Michael Isakoff, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2014
• Primary Completion (ACTUAL): June 30, 2015
• Study Completion (ACTUAL): March 31, 2020

Study Registration Dates

• First Submitted: March 24, 2014
• First Submitted That Met QC Criteria: March 24, 2014
• First Posted (ESTIMATE): March 27, 2014

Study Record Updates

• Last Update Posted (ACTUAL): May 19, 2020
• Last Update Submitted That Met QC Criteria: May 4, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Recurrence; Osteosarcoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Halichondrin B
• Other Study ID Numbers: NCI-2014-00621 (REGISTRY: CTRP (Clinical Trial Reporting Program)); U10CA180886 (U.S. NIH Grant/Contract); U10CA098543 (U.S. NIH Grant/Contract); COG-AOST1322; AOST1322 (OTHER: CTEP)