Glembatumumab Vedotin in Treating Patients With Recurrent or Refractory Osteosarcoma
- Conditions
- Recurrent Osteosarcoma
- Interventions
- Registration Number
- NCT02487979
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase II trial studies how well glembatumumab vedotin works in treating patients with osteosarcoma that has come back (recurrent) or does not respond to treatment (refractory). Monoclonal antibodies, such as glembatumumab vedotin, may find tumor cells and help kill them.
- Detailed Description
PRIMARY OBJECTIVES:
I. To estimate whether CDX-011 (glembatumumab vedotin) therapy either increases the disease control rate at 4 months in patients with recurrent measurable osteosarcoma as compared to an historical Children's Oncology Group (COG) experience or produces an objective response rate in patients without previous eribulin (eribulin mesylate) treatment.
SECONDARY OBJECTIVES:
I. To assess the feasibility and toxicity profile of CDX-011 in patients with recurrent osteosarcoma.
II. To describe the pharmacokinetics of CDX-011 in adolescents and young adults with recurrent osteosarcoma enrolled at COG sites and COG phase I consortium sites only.
III. To determine if there is a relationship between tumor GPNMB expression by immunohistochemistry (IHC) and response to CDX-011 therapy.
IV. To estimate, in the cohort of patients previously treated with eribulin, the proportion who will experience disease progression during the first 4 months of CDX-011 therapy and the proportion of patients who experience a Response Evaluation Criteria in Solid Tumors (RECIST)-defined complete or partial response.
OUTLINE:
Patients receive glembatumumab vedotin intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 22
-
Patients must have had histologic verification of osteosarcoma at original diagnosis or relapse
-
Patients must have measurable disease according to RECIST 1.1, and have relapsed or become refractory to conventional therapy
-
Patient must have archival tumor specimen available for submission
-
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 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 (4 weeks if prior nitrosourea)
- Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent
- Radiation therapy (RT): >= 2 weeks 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
- Monoclonal antibodies: must not have received any monoclonal based therapies within 4 weeks, and all other immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) within 2 weeks, prior to study enrollment
-
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:
- Age 1 to < 2 years (male and female: 0.6 mg/dL)
- Age 2 to < 6 years (male and female: 0.8 mg/dL)
- Age 6 to < 10 years (male and female: 1 mg/dL)
- Age 10 to < 13 years (male and female: 1.2 mg/dL)
- Age 13 to < 16 years (male: 1.5 mg/dL and female: 1.4 mg/dL)
- Age >= 16 (male: 1.7 mg/dL and female: 1.4 mg/dL)
-
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
-
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 110 U/L; for the purposes of this study the ULN for SGPT is defined as 45 U/L
-
Serum albumin > 2 g/dL
-
Shortening fraction of >= 27% by echocardiogram, or
-
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 > grade 2 neuropathy according to the Modified ("Balis") Pediatric Scale of Peripheral Neuropathies will be excluded except in cases in which neuropathy is secondary to prior surgery
- Patients who have previously received CDX-011 (CR011-vc monomethyl auristatin E [MMAE]; CDX-011) or other MMAE-containing agents
- Patients who have received other investigational drugs within 2 weeks or 5 half-lives (whichever is longer) prior to study enrollment
- Patients with a history of allergic reactions attributed to compounds of similar composition to dolastatin or auristatin; compounds of similar composition include auristatin PHE as an anti-fungal agent, auristatin PE (TZT-1027, Soblidotin, NSC-654663) as an anti-tumor agent and symplostatin 1 as an anti-tumor agent
- Patients with known central nervous system metastasis are not eligible
- Patients who have had major surgery within 2 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
- 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 and for 2 months after the end of study treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (glembatumumab vedotin) Glembatumumab Vedotin Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Treatment (glembatumumab vedotin) Laboratory Biomarker Analysis Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Treatment (glembatumumab vedotin) Pharmacological Study Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Disease Control Success First six cycles (21-day cycle) of protocol therapy The number of patients who do not experience disease progression or death in the six cycles following enrollment on AOST1521
- Secondary Outcome Measures
Name Time Method Toxicity Associated With Chemotherapy Duration of protocol therapy - Up to two years The number of cycles aggregated across all patients where CTC Version 4 grade 3 or higher.
Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Half-life Baseline to 24 hours post infusion on course 1 Total antibody and antibody-drug conjugate half-life are estimated from the sampling time points: Before first dose (Baseline), end of infusion, at 1, 2, 4, and 24 hours post infusion
Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Clearance Baseline to 24 hours post infusion on course 1 Total antibody and antibody-drug conjugate clearance are estimated from the sampling time points: Before first dose (Baseline), end of infusion, at 1, 2, 4, and 24 hours post infusion
Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Areas Under the Curve Baseline to 24 hours post infusion on course 1 Total antibody and antibody-drug conjugate areas under the curve are estimated from the sampling time points: Before first dose (Baseline), end of infusion, at 1, 2, 4, and 24 hours post infusion
Number of Participants With Glycoprotein NMB (GPNMB) Expression Stratified by Immunohistochemistry (IHC) Staining Strength Prior to the time of enrollment GPNMB expression by IHC of 0+ to 3+ staining strength as assessed on archived tumor specimens. 0 being no GPNMB expression and 3 indicating strong GPNMB expression.
RECIST Response First six cycles (21-day cycle) of protocol therapy The number of patients who experience a complete or partial response according the RECIST criteria for target lesions complete response (CR) disappearance of all lesions; partial response (PR ) \>= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+PR.
Trial Locations
- Locations (155)
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Golisano Children's Hospital of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
University of Washington Medical Center - Montlake
🇺🇸Seattle, Washington, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Cancer and Blood Specialists-Shadow
🇺🇸Las Vegas, Nevada, United States
Radiation Oncology Centers of Nevada Central
🇺🇸Las Vegas, Nevada, United States
Cancer Therapy and Integrative Medicine
🇺🇸Las Vegas, Nevada, United States
21st Century Oncology-Vegas Tenaya
🇺🇸Las Vegas, Nevada, United States
HealthCare Partners Medical Group Oncology/Hematology-Tenaya
🇺🇸Las Vegas, Nevada, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada-Summerlin
🇺🇸Las Vegas, Nevada, United States
Summerlin Hospital Medical Center
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Las Vegas Cancer Center-Medical Center
🇺🇸Las Vegas, Nevada, United States
21st Century Oncology-Fort Apache
🇺🇸Las Vegas, Nevada, United States
HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
🇺🇸Las Vegas, Nevada, United States
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
University Hospital
🇺🇸San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Saint Mary's Regional Medical Center
🇺🇸Reno, Nevada, United States
Albany Medical Center
🇺🇸Albany, New York, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
NYU Winthrop Hospital
🇺🇸Mineola, New York, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸New York, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Children's Oncology Group
🇺🇸Philadelphia, Pennsylvania, United States
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Vanderbilt Breast Center at One Hundred Oaks
🇺🇸Nashville, Tennessee, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
Vanderbilt-Ingram Cancer Center Cool Springs
🇺🇸Franklin, Tennessee, United States
Saint Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸Houston, Texas, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Dell Children's Medical Center of Central Texas
🇺🇸Austin, Texas, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
University Pediatric Hospital
🇵🇷San Juan, Puerto Rico
Centre Hospitalier Universitaire de Quebec
🇨🇦Quebec, Canada
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
Banner University Medical Center - Tucson
🇺🇸Tucson, Arizona, United States
Kaiser Permanente-Anaheim
🇺🇸Anaheim, California, United States
University of Arizona Cancer Center-North Campus
🇺🇸Tucson, Arizona, United States
PCR Oncology
🇺🇸Arroyo Grande, California, United States
Kaiser Permanente-Fontana
🇺🇸Fontana, California, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Mattel Children's Hospital UCLA
🇺🇸Los Angeles, California, United States
Kaiser Permanente-San Diego Zion
🇺🇸San Diego, California, United States
UCSF Medical Center-Mission Bay
🇺🇸San Francisco, California, United States
Smilow Cancer Center/Yale-New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
Saint Mary's Hospital
🇺🇸West Palm Beach, Florida, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸Atlanta, Georgia, United States
Saint Luke's Cancer Institute - Boise
🇺🇸Boise, Idaho, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
IU Health North Hospital
🇺🇸Carmel, Indiana, United States
The Carle Foundation Hospital
🇺🇸Urbana, Illinois, United States
Lake Huron Medical Center
🇺🇸Port Huron, Michigan, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Ascension Saint John Hospital
🇺🇸Detroit, Michigan, United States
University of Minnesota/Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Delbert Day Cancer Institute at PCRMC
🇺🇸Rolla, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Mercy Hospital Washington
🇺🇸Washington, Missouri, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
Carson Tahoe Regional Medical Center
🇺🇸Carson City, Nevada, United States
21st Century Oncology-Henderson
🇺🇸Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada-Southeast Henderson
🇺🇸Henderson, Nevada, United States
21st Century Oncology
🇺🇸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
Saint Louis Cancer and Breast Institute-Ballwin
🇺🇸Ballwin, Missouri, United States
Children's Mercy Hospitals and Clinics
🇺🇸Kansas City, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Children's Hospital at Montefiore
🇺🇸Bronx, New York, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Ann M Wierman MD LTD
🇺🇸Las Vegas, Nevada, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
🇺🇸Denver, Colorado, United States
C S Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸Tampa, Florida, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Kaiser Permanente-Bellflower
🇺🇸Bellflower, California, United States
Kaiser Permanente Downey Medical Center
🇺🇸Downey, California, United States
Valley Children's Hospital
🇺🇸Madera, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸Palo Alto, California, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
Kaiser Permanente-Capitol Hill Medical Center
🇺🇸Washington, District of Columbia, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
University of Florida Health Science Center - Gainesville
🇺🇸Gainesville, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Rush - Copley Medical Center
🇺🇸Aurora, Illinois, United States
Lurie Children's Hospital-Chicago
🇺🇸Chicago, Illinois, United States
Carle on Vermilion
🇺🇸Danville, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
Memorial Hospital of South Bend
🇺🇸South Bend, Indiana, United States
Rush-Copley Healthcare Center
🇺🇸Yorkville, Illinois, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Ochsner Medical Center Jefferson
🇺🇸New Orleans, Louisiana, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Saint Louis Cancer and Breast Institute-South City
🇺🇸Saint Louis, Missouri, United States
Cancer and Blood Specialists-Henderson
🇺🇸Henderson, Nevada, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Comprehensive Cancer Centers of Nevada - Henderson
🇺🇸Henderson, Nevada, United States
Las Vegas Cancer Center-Henderson
🇺🇸Henderson, Nevada, United States
Radiation Oncology Centers of Nevada Southeast
🇺🇸Las Vegas, Nevada, United States
Cancer and Blood Specialists-Tenaya
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Northwest
🇺🇸Las Vegas, Nevada, United States
OptumCare Cancer Care at Fort Apache
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Central Valley
🇺🇸Las Vegas, Nevada, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
🇺🇸Toledo, Ohio, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Montefiore Medical Center-Weiler Hospital
🇺🇸Bronx, New York, United States
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
The Montreal Children's Hospital of the MUHC
🇨🇦Montreal, Quebec, Canada
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Montefiore Medical Center-Einstein Campus
🇺🇸Bronx, New York, United States
Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States