Glembatumumab Vedotin in Treating Patients With Recurrent or Refractory Osteosarcoma

NCT ID: NCT02487979

Last Updated: 2022-01-18

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-16

Study Completion Date

2021-12-31

Brief Summary

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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

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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.

Conditions

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Recurrent Osteosarcoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (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.

Group Type EXPERIMENTAL

Glembatumumab Vedotin

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Interventions

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Glembatumumab Vedotin

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Pharmacological Study

Correlative studies

Intervention Type OTHER

Other Intervention Names

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Antibody-Drug Conjugate CR011-vcMMAE CDX-011 CR011-vcMMAE CR011-vcMMAE Immunotoxin

Eligibility Criteria

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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
Minimum Eligible Age

12 Years

Maximum Eligible Age

49 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lisa M Kopp

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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Children's Hospital of Alabama

Birmingham, Alabama, United States

Site Status

Banner University Medical Center - Tucson

Tucson, Arizona, United States

Site Status

University of Arizona Cancer Center-North Campus

Tucson, Arizona, United States

Site Status

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

Kaiser Permanente-Anaheim

Anaheim, California, United States

Site Status

PCR Oncology

Arroyo Grande, California, United States

Site Status

Kaiser Permanente-Bellflower

Bellflower, California, United States

Site Status

Kaiser Permanente Downey Medical Center

Downey, California, United States

Site Status

Kaiser Permanente-Fontana

Fontana, California, United States

Site Status

Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Site Status

Mattel Children's Hospital UCLA

Los Angeles, California, United States

Site Status

Valley Children's Hospital

Madera, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

Site Status

Kaiser Permanente-San Diego Zion

San Diego, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

University of Colorado Hospital

Aurora, Colorado, United States

Site Status

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, United States

Site Status

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Site Status

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Kaiser Permanente-Capitol Hill Medical Center

Washington D.C., District of Columbia, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Site Status

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

Site Status

University of Florida Health Science Center - Gainesville

Gainesville, Florida, United States

Site Status

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States

Site Status

Nicklaus Children's Hospital

Miami, Florida, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

Site Status

Nemours Children's Hospital

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

Site Status

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Site Status

Tampa General Hospital

Tampa, Florida, United States

Site Status

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, United States

Site Status

Saint Mary's Hospital

West Palm Beach, Florida, United States

Site Status

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States

Site Status

Saint Luke's Cancer Institute - Boise

Boise, Idaho, United States

Site Status

Rush - Copley Medical Center

Aurora, Illinois, United States

Site Status

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Carle on Vermilion

Danville, Illinois, United States

Site Status

Carle Physician Group-Effingham

Effingham, Illinois, United States

Site Status

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, United States

Site Status

Saint Jude Midwest Affiliate

Peoria, Illinois, United States

Site Status

Carle Cancer Center

Urbana, Illinois, United States

Site Status

The Carle Foundation Hospital

Urbana, Illinois, United States

Site Status

Rush-Copley Healthcare Center

Yorkville, Illinois, United States

Site Status

IU Health North Hospital

Carmel, Indiana, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Memorial Hospital of South Bend

South Bend, Indiana, United States

Site Status

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Site Status

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States

Site Status

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Site Status

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Ascension Saint John Hospital

Detroit, Michigan, United States

Site Status

Lake Huron Medical Center

Port Huron, Michigan, United States

Site Status

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Saint Louis Cancer and Breast Institute-Ballwin

Ballwin, Missouri, United States

Site Status

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Site Status

Delbert Day Cancer Institute at PCRMC

Rolla, Missouri, United States

Site Status

Mercy Hospital Springfield

Springfield, Missouri, United States

Site Status

CoxHealth South Hospital

Springfield, Missouri, United States

Site Status

Saint Louis Cancer and Breast Institute-South City

St Louis, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Site Status

Mercy Hospital Washington

Washington, Missouri, United States

Site Status

Carson Tahoe Regional Medical Center

Carson City, Nevada, United States

Site Status

Cancer and Blood Specialists-Henderson

Henderson, Nevada, United States

Site Status

Comprehensive Cancer Centers of Nevada - Henderson

Henderson, Nevada, United States

Site Status

Las Vegas Cancer Center-Henderson

Henderson, Nevada, United States

Site Status

21st Century Oncology-Henderson

Henderson, Nevada, United States

Site Status

Comprehensive Cancer Centers of Nevada-Southeast Henderson

Henderson, Nevada, United States

Site Status

Cancer and Blood Specialists-Shadow

Las Vegas, Nevada, United States

Site Status

Radiation Oncology Centers of Nevada Central

Las Vegas, Nevada, United States

Site Status

21st Century Oncology

Las Vegas, Nevada, United States

Site Status

HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway

Las Vegas, Nevada, United States

Site Status

HealthCare Partners Medical Group Oncology/Hematology-San Martin

Las Vegas, Nevada, United States

Site Status

Radiation Oncology Centers of Nevada Southeast

Las Vegas, Nevada, United States

Site Status

Cancer Therapy and Integrative Medicine

Las Vegas, Nevada, United States

Site Status

21st Century Oncology-Vegas Tenaya

Las Vegas, Nevada, United States

Site Status

Ann M Wierman MD LTD

Las Vegas, Nevada, United States

Site Status

Cancer and Blood Specialists-Tenaya

Las Vegas, Nevada, United States

Site Status

Comprehensive Cancer Centers of Nevada - Northwest

Las Vegas, Nevada, United States

Site Status

HealthCare Partners Medical Group Oncology/Hematology-Tenaya

Las Vegas, Nevada, United States

Site Status

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, United States

Site Status

Comprehensive Cancer Centers of Nevada-Summerlin

Las Vegas, Nevada, United States

Site Status

Summerlin Hospital Medical Center

Las Vegas, Nevada, United States

Site Status

Las Vegas Cancer Center-Medical Center

Las Vegas, Nevada, United States

Site Status

21st Century Oncology-Fort Apache

Las Vegas, Nevada, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

OptumCare Cancer Care at Fort Apache

Las Vegas, Nevada, United States

Site Status

HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills

Las Vegas, Nevada, United States

Site Status

Comprehensive Cancer Centers of Nevada - Central Valley

Las Vegas, Nevada, United States

Site Status

Renown Regional Medical Center

Reno, Nevada, United States

Site Status

Saint Mary's Regional Medical Center

Reno, Nevada, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Albany Medical Center

Albany, New York, United States

Site Status

NYU Winthrop Hospital

Mineola, New York, United States

Site Status

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Site Status

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

State University of New York Upstate Medical University

Syracuse, New York, United States

Site Status

Montefiore Medical Center-Einstein Campus

The Bronx, New York, United States

Site Status

Montefiore Medical Center-Weiler Hospital

The Bronx, New York, United States

Site Status

Children's Hospital at Montefiore

The Bronx, New York, United States

Site Status

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

Site Status

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Dayton Children's Hospital

Dayton, Ohio, United States

Site Status

ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

Toledo, Ohio, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Oncology Group

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

Site Status

Vanderbilt-Ingram Cancer Center Cool Springs

Franklin, Tennessee, United States

Site Status

East Tennessee Childrens Hospital

Knoxville, Tennessee, United States

Site Status

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, United States

Site Status

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States

Site Status

Cancer Therapy and Research Center at The UT Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

University Hospital

San Antonio, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

University of Washington Medical Center - Montlake

Seattle, Washington, United States

Site Status

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States

Site Status

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Alberta Children's Hospital

Calgary, Alberta, Canada

Site Status

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire de Quebec

Québec, , Canada

Site Status

University Pediatric Hospital

San Juan, , Puerto Rico

Site Status

Countries

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United States Canada Puerto Rico

References

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Kopp LM, Malempati S, Krailo M, Gao Y, Buxton A, Weigel BJ, Hawthorne T, Crowley E, Moscow JA, Reid JM, Villalobos V, Randall RL, Gorlick R, Janeway KA. Phase II trial of the glycoprotein non-metastatic B-targeted antibody-drug conjugate, glembatumumab vedotin (CDX-011), in recurrent osteosarcoma AOST1521: A report from the Children's Oncology Group. Eur J Cancer. 2019 Nov;121:177-183. doi: 10.1016/j.ejca.2019.08.015. Epub 2019 Oct 3.

Reference Type DERIVED
PMID: 31586757 (View on PubMed)

Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

Reference Type DERIVED
PMID: 31401903 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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NCI-2015-01037

Identifier Type: REGISTRY

Identifier Source: secondary_id

AOST1521

Identifier Type: -

Identifier Source: secondary_id

s16-01136

Identifier Type: -

Identifier Source: secondary_id

AOST1521

Identifier Type: OTHER

Identifier Source: secondary_id

AOST1521

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180886

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2015-01037

Identifier Type: -

Identifier Source: org_study_id

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