Eribulin Mesylate in Treating Patients With Recurrent or Refractory Osteosarcoma
- Conditions
- Recurrent Osteosarcoma
- Interventions
- Other: Pharmacological Study
- Registration Number
- NCT02097238
- Lead Sponsor
- National Cancer Institute (NCI)
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 19
-
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
-
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (eribulin mesylate) Pharmacological Study 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. Treatment (eribulin mesylate) 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.
- Primary Outcome Measures
Name Time Method Response Evaluation Criteria in Solid Tumors (RECIST) Response 4 months 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.
Disease Control Success 4 Months The number of patients who do not experience disease progression or death in the four months following enrollment on AOST1322.
- Secondary Outcome Measures
Name Time Method Number of Cycles Where a Dose Limiting Toxicity Was Identified 4 months 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.
Area Under the Curve 0-infinity of Eribulin Mesylate in Ng-hr/ml 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 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.
Clearance of Eribulin Mesylate in L/hr 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. 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.
A Half Life of Eribulin Mesylate in hr 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 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.
Trial Locations
- Locations (119)
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Saint Vincent Hospital and Health Care Center
🇺🇸Indianapolis, Indiana, United States
Children's Specialty Center of Nevada II
🇺🇸Las Vegas, Nevada, United States
HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Northwest
🇺🇸Las Vegas, Nevada, United States
HealthCare Partners Medical Group Oncology/Hematology-Tenaya
🇺🇸Las Vegas, Nevada, United States
Las Vegas Cancer Center-Medical Center
🇺🇸Las Vegas, Nevada, United States
Cancer and Blood Specialists-Fort Apache
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Central Valley
🇺🇸Las Vegas, Nevada, United States
21st Century Oncology - Vegas Tenaya
🇺🇸Las Vegas, Nevada, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
University of Minnesota Medical Center-Fairview
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Cancer Therapy and Integrative Medicine
🇺🇸Las Vegas, Nevada, United States
Palmetto Health Richland
🇺🇸Columbia, South Carolina, United States
Cancer and Blood Specialists-Tenaya
🇺🇸Las Vegas, Nevada, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
Radiation Oncology Centers of Nevada Southeast
🇺🇸Las Vegas, Nevada, United States
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
HealthCare Partners Medical Group Oncology/Hematology-San Martin
🇺🇸Las Vegas, Nevada, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
Lurie Children's Hospital-Chicago
🇺🇸Chicago, Illinois, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸Atlanta, Georgia, United States
Saint Mary's Hospital
🇺🇸West Palm Beach, Florida, United States
Memorial University Medical Center
🇺🇸Savannah, Georgia, United States
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States
Good Samaritan Regional Health Center
🇺🇸Mount Vernon, Illinois, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Maine Children's Cancer Program
🇺🇸Scarborough, Maine, United States
Michigan State University Clinical Center
🇺🇸East Lansing, Michigan, United States
Essentia Health Cancer Center
🇺🇸Duluth, Minnesota, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Central Care Cancer Center-Carrie J Babb Cancer Center
🇺🇸Bolivar, Missouri, United States
Mercy Hospital-Joplin
🇺🇸Joplin, Missouri, United States
Freeman Health System
🇺🇸Joplin, Missouri, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
Las Vegas Cancer Center-Henderson
🇺🇸Henderson, Nevada, United States
Cancer and Blood Specialists-Henderson
🇺🇸Henderson, Nevada, United States
Radiation Oncology Centers of Nevada Central
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada-Southeast Henderson
🇺🇸Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada - Henderson
🇺🇸Henderson, Nevada, United States
21st Century Oncology - Henderson
🇺🇸Henderson, Nevada, United States
Cancer and Blood Specialists-Shadow
🇺🇸Las Vegas, Nevada, United States
Nevada Cancer Research Foundation CCOP
🇺🇸Las Vegas, Nevada, United States
21st Century Oncology
🇺🇸Las Vegas, Nevada, United States
Summerlin Hospital Medical Center
🇺🇸Las Vegas, Nevada, United States
21st Century Oncology - Fort Apache
🇺🇸Las Vegas, Nevada, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸New Hyde Park, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
Sanford Medical Center-Fargo
🇺🇸Fargo, North Dakota, United States
The Toledo Hospital/Toledo Children's Hospital
🇺🇸Toledo, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸Bethlehem, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Children's Hospital of San Antonio
🇺🇸San Antonio, Texas, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Childrens Hospital-King's Daughters
🇺🇸Norfolk, Virginia, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, United States
West Virginia University Healthcare
🇺🇸Morgantown, West Virginia, United States
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
Southern California Permanente Medical Group
🇺🇸Downey, California, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸Palo Alto, California, United States
Mattel Children's Hospital UCLA
🇺🇸Los Angeles, California, United States
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
Children's Hospital Central California
🇺🇸Madera, California, United States
Children's Hospital and Research Center at Oakland
🇺🇸Oakland, California, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
🇺🇸Denver, Colorado, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸Tampa, Florida, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Children's Hospital and Medical Center of Omaha
🇺🇸Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Legacy Emanuel Children's Hospital
🇺🇸Portland, Oregon, United States
Phelps County Regional Medical Center
🇺🇸Rolla, Missouri, United States
Saint John's Clinic-Rolla-Cancer and Hematology
🇺🇸Rolla, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Advocate Children's Hospital-Oak Lawn
🇺🇸Oak Lawn, Illinois, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
Siouxland Regional Cancer Center
🇺🇸Sioux City, Iowa, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
CoxHealth Cancer Center
🇺🇸Branson, Missouri, United States
Saint Louis Cancer and Breast Institute-South City
🇺🇸Saint Louis, Missouri, United States
Comprehensive Cancer Centers of Nevada-Summerlin
🇺🇸Las Vegas, Nevada, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Mission Hospital-Memorial Campus
🇺🇸Asheville, North Carolina, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
The Childrens Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Ochsner Medical Center Jefferson
🇺🇸New Orleans, Louisiana, United States