Clinical trial NCT02097238: Eribulin Mesylate in Treating Patients With Recurrent or Refractory Osteosarcoma
Official title: A Phase II Study of Eribulin (NSC# 707389) in Recurrent or Refractory Osteosarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Osteosarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2014-03-27
Enrollment: 19
Sex: ALL
Minimum age (years): 12
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Disease Control Success
timeFrame: 4 Months
measure: Response Evaluation Criteria in Solid Tumors (RECIST) Response
timeFrame: 4 months
Secondary outcomes:
measure: Number of Cycles Where a Dose Limiting Toxicity Was Identified
timeFrame: 4 months
measure: Area Under the Curve 0-infinity of Eribulin Mesylate in Ng-hr/ml
timeFrame: 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
measure: Clearance of Eribulin Mesylate in L/hr
timeFrame: 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.
measure: A Half Life of Eribulin Mesylate in hr
timeFrame: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Downey
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Mattel Children's Hospital UCLA
state: California
city: Madera
country: United States
facility: Children's Hospital Central California
state: California
city: Oakland
country: United States
facility: Children's Hospital and Research Center at Oakland
state: California
city: Oakland
country: United States
facility: Kaiser Permanente-Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital Stanford University
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Nemours Children's Clinic-Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Cancer Center
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's Clinic - Pensacola
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: Saint Joseph's Hospital/Children's Hospital-Tampa
state: Florida
city: West Palm Beach
country: United States
facility: Saint Mary's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Egleston
state: Georgia
city: Savannah
country: United States
facility: Memorial University Medical Center
state: Georgia
city: Chicago
country: United States
facility: Lurie Children's Hospital-Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Mount Vernon
country: United States
facility: Good Samaritan Regional Health Center
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Children's Hospital-Oak Lawn
state: Illinois
city: Peoria
country: United States
facility: Saint Jude Midwest Affiliate
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Indianapolis
country: United States
facility: Saint Vincent Hospital and Health Care Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Regional Cancer Center
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center Jefferson
state: Louisiana
city: Scarborough
country: United States
facility: Maine Children's Cancer Program
state: Maine
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University Clinical Center
state: Michigan
city: Duluth
country: United States
facility: Essentia Health Cancer Center
state: Minnesota
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center-Fairview
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Bolivar
country: United States
facility: Central Care Cancer Center-Carrie J Babb Cancer Center
state: Missouri
city: Branson
country: United States
facility: CoxHealth Cancer Center
state: Missouri
city: Joplin
country: United States
facility: Freeman Health System
state: Missouri
city: Joplin
country: United States
facility: Mercy Hospital-Joplin
state: Missouri
city: Kansas City
country: United States
facility: The Childrens Mercy Hospital
state: Missouri
city: Rolla
country: United States
facility: Phelps County Regional Medical Center
state: Missouri
city: Rolla
country: United States
facility: Saint John's Clinic-Rolla-Cancer and Hematology
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis Cancer and Breast Institute-South City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Springfield
country: United States
facility: CoxHealth South Hospital
state: Missouri
city: Omaha
country: United States
facility: Children's Hospital and Medical Center of Omaha
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Henderson
country: United States
facility: Cancer and Blood Specialists-Henderson
state: Nevada
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada - Henderson
state: Nevada
city: Henderson
country: United States
facility: Las Vegas Cancer Center-Henderson
state: Nevada
city: Henderson
country: United States
facility: 21st Century Oncology - Henderson
state: Nevada
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada-Southeast Henderson
state: Nevada
city: Las Vegas
country: United States
facility: Cancer and Blood Specialists-Shadow
state: Nevada
city: Las Vegas
country: United States
facility: Nevada Cancer Research Foundation CCOP
state: Nevada
city: Las Vegas
country: United States
facility: Radiation Oncology Centers of Nevada Central
state: Nevada
city: Las Vegas
country: United States
facility: 21st Century Oncology
state: Nevada
city: Las Vegas
country: United States
facility: Children's Specialty Center of Nevada II
state: Nevada
city: Las Vegas
country: United States
facility: HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
state: Nevada
city: Las Vegas
country: United States
facility: HealthCare Partners Medical Group Oncology/Hematology-San Martin
state: Nevada
city: Las Vegas
country: United States
facility: Radiation Oncology Centers of Nevada Southeast
state: Nevada
city: Las Vegas
country: United States
facility: Cancer Therapy and Integrative Medicine
state: Nevada
city: Las Vegas
country: United States
facility: Cancer and Blood Specialists-Tenaya
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada - Northwest
state: Nevada
city: Las Vegas
country: United States
facility: HealthCare Partners Medical Group Oncology/Hematology-Tenaya
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada-Summerlin
state: Nevada
city: Las Vegas
country: United States
facility: Summerlin Hospital Medical Center
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas Cancer Center-Medical Center
state: Nevada
city: Las Vegas
country: United States
facility: 21st Century Oncology - Fort Apache
state: Nevada
city: Las Vegas
country: United States
facility: Cancer and Blood Specialists-Fort Apache
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada - Central Valley
state: Nevada
city: Las Vegas
country: United States
facility: 21st Century Oncology - Vegas Tenaya
state: Nevada
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: New Hyde Park
country: United States
facility: The Steven and Alexandra Cohen Children's Medical Center of New York
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Asheville
country: United States
facility: Mission Hospital-Memorial Campus
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Fargo
country: United States
facility: Sanford Medical Center-Fargo
state: North Dakota
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Childrens Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Toledo
country: United States
facility: The Toledo Hospital/Toledo Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Legacy Emanuel Children's Hospital
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Bethlehem
country: United States
facility: Lehigh Valley Hospital - Muhlenberg
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Columbia
country: United States
facility: Palmetto Health Richland
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center - Sioux Falls
state: South Dakota
city: Knoxville
country: United States
facility: East Tennessee Childrens Hospital
state: Tennessee
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Children's Hospital of San Antonio
state: Texas
city: Norfolk
country: United States
facility: Childrens Hospital-King's Daughters
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center and Children's Hospital
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Healthcare
state: West Virginia
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
Study officials:
affiliation: Children's Oncology Group
name: Michael Isakoff
role: PRINCIPAL_INVESTIGATOR
References: