Glembatumumab Vedotin in Treating Patients With Recurrent or Refractory Osteosarcoma

Recurrent Osteosarcoma Clinical Trial

Official title:

A Phase 2 Study of GPNMB-Targeted Antibody-Drug Conjugate, CDX-011 (Glembatumumab Vedotin, CR011-vcMMAE; NSC# 763737), in Recurrent or Refractory Osteosarcoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02487979
• Other study ID #: NCI-2015-01037
• Secondary ID: NCI-2015-01037AO
• Status: Completed
• Phase: Phase 2
• Start date: February 16, 2016
• Est. completion date: December 31, 2021

Study information

• Verified date: January 2022
• 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 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.

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 information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: December 31, 2021
• Est. primary completion date: June 30, 2017
• 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 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Osteosarcoma
• Recurrent Osteosarcoma

Intervention

Drug:
• Glembatumumab Vedotin
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Pharmacological Study
Correlative studies

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	The Montreal Children's Hospital of the MUHC	Montreal	Quebec
Canada	Centre Hospitalier Universitaire de Quebec	Quebec
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Puerto Rico	University Pediatric Hospital	San Juan
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Albany Medical Center	Albany	New York
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	PCR Oncology	Arroyo Grande	California
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	University of Colorado Hospital	Aurora	Colorado
United States	Dell Children's Medical Center of Central Texas	Austin	Texas
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	Children's Hospital of Alabama	Birmingham	Alabama
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Children's Hospital at Montefiore	Bronx	New York
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	IU Health North Hospital	Carmel	Indiana
United States	Carson Tahoe Regional Medical Center	Carson City	Nevada
United States	Lurie Children's Hospital-Chicago	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Medical City Dallas Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Carle on Vermilion	Danville	Illinois
United States	Dayton Children's Hospital	Dayton	Ohio
United States	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Kaiser Permanente Downey Medical Center	Downey	California
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Kaiser Permanente-Fontana	Fontana	California
United States	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Vanderbilt-Ingram Cancer Center Cool Springs	Franklin	Tennessee
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Hackensack University Medical Center	Hackensack	New Jersey
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/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Riley Hospital for Children	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	Children's Mercy Hospitals and Clinics	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	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Ann M Wierman MD LTD	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	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	OptumCare Cancer Care at Fort Apache	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	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Mattel Children's Hospital UCLA	Los Angeles	California
United States	Valley Children's Hospital	Madera	California
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Saint Jude Children's Research Hospital	Memphis	Tennessee
United States	Nicklaus Children's Hospital	Miami	Florida
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	NYU Winthrop Hospital	Mineola	New York
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
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	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	Children's Hospital of Orange County	Orange	California
United States	AdventHealth Orlando	Orlando	Florida
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	Children's Oncology Group	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Oregon Health and Science University	Portland	Oregon
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
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	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida
United States	Cancer Therapy and Research Center at The UT Health Science Center at San Antonio	San Antonio	Texas
United States	Methodist Children's Hospital of South Texas	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	Kaiser Permanente-San Diego Zion	San Diego	California
United States	Rady Children's Hospital - San Diego	San Diego	California
United States	UCSF Medical Center-Mission Bay	San Francisco	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Seattle Children's Hospital	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Memorial Hospital of South Bend	South Bend	Indiana
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	Tampa General Hospital	Tampa	Florida
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Children's National Medical Center	Washington	District of Columbia
United States	Kaiser Permanente-Capitol Hill Medical Center	Washington	District of Columbia
United States	Mercy Hospital Washington	Washington	Missouri
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Saint Mary's Hospital	West Palm Beach	Florida
United States	Alfred I duPont Hospital for Children	Wilmington	Delaware
United States	Rush-Copley Healthcare Center	Yorkville	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

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 six cycles following enrollment on AOST1521	First six cycles (21-day cycle) of protocol therapy
Secondary	Toxicity Associated With Chemotherapy	The number of cycles aggregated across all patients where CTC Version 4 grade 3 or higher.	Duration of protocol therapy - Up to two years
Secondary	Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Half-life	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	Baseline to 24 hours post infusion on course 1
Secondary	Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Clearance	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	Baseline to 24 hours post infusion on course 1
Secondary	Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Areas Under the Curve	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	Baseline to 24 hours post infusion on course 1
Secondary	Number of Participants With Glycoprotein NMB (GPNMB) Expression Stratified by Immunohistochemistry (IHC) Staining Strength	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.	Prior to the time of enrollment
Secondary	RECIST Response	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.	First six cycles (21-day cycle) of protocol therapy