Eribulin Mesylate in Treating Patients With Recurrent or Refractory Osteosarcoma

Recurrent Osteosarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02097238
• Other study ID #: NCI-2014-00621
• Secondary ID: NCI-2014-00621CO
• Status: Completed
• Phase: Phase 2
• Start date: August 2014
• Est. completion date: March 31, 2020

Study information

• Verified date: May 2020
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: March 31, 2020
• Est. primary completion date: June 30, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 49 Years

Eligibility

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

Related Conditions & MeSH terms

• Osteosarcoma
• Recurrent Osteosarcoma

Intervention

Drug:
• Eribulin Mesylate
Given IV

Other:
• Pharmacological Study
Correlative studies

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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.
Secondary	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