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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02484443
Other study ID # NCI-2015-01001
Secondary ID NCI-2015-01001AO
Status Completed
Phase Phase 2
First received
Last updated
Start date February 4, 2016
Est. completion date September 30, 2023

Study information

Verified date October 2023
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This phase II trial studies how well dinutuximab works when given with sargramostim in treating patients with osteosarcoma that has come back after treatment (recurrent). Monoclonal antibodies, such as dinutuximab, may find tumor cells and help kill them. Sargramostim may help the body increase the amount of white blood cells it produces, which help the body fight off infections. Giving dinutuximab with sargramostim may work better and kill more cancer cells.


Description:

PRIMARY OBJECTIVES: I. To determine the disease control rate in patients with completely resected recurrent osteosarcoma treated with ch14.18 (dinutuximab) in combination with sargramostim (granulocyte-macrophage colony-stimulating factor [GM-CSF]) as compared to historical Children's Oncology Group (COG) experience. SECONDARY OBJECTIVES: I. To characterize the pharmacokinetics of ch14.18 (dinutuximab) in patients with recurrent osteosarcoma. II. To determine the occurrence of unacceptable toxicity (UT) in patients with recurrent osteosarcoma treated with ch14.18 (dinutuximab) in combination with sargramostim. III. To assess the relationship between probability of disease control and tumor ganglioside GD2 (GD2) expression. TERTIARY OBJECTIVES: I. To assess the relationship between probability of disease control and tumor GD2 expression. II. To assess KIR and Fcgamma receptor (FcgammaR) genotypes, NKp30 isoforms and its circulating ligand, B7-H6, and their relationships to the probability of disease control. III. To attempt banking of tumor samples for future research studies from patients enrolled on study who undergo biopsy or resection of suspected metastatic disease recurrence while on protocol therapy or during the evaluation period. IV. To determine a descriptive profile of human anti-chimeric antibody (HACA) during immunotherapy. V. To bank serial plasma samples for future studies of circulating tumor deoxyribonucleic acid (ctDNA) detection as a marker of disease progression and response. OUTLINE: Patients receive sargramostim subcutaneously (SC) once daily (QD) on days 1-14 and dinutuximab intravenously (IV) over 10 hours on days 4-7 (dinutuximab infusion may be extended up to a total of 20 hours per day for anticipated toxicities). Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 8 and 12 months.


Recruitment information / eligibility

Status Completed
Enrollment 41
Est. completion date September 30, 2023
Est. primary completion date March 31, 2020
Accepts healthy volunteers No
Gender All
Age group N/A to 29 Years
Eligibility Inclusion Criteria: - Patients must have histologic diagnosis of osteosarcoma at original diagnosis - Patients must have had at least one episode of disease recurrence in the lungs without limitation on number of episodes of recurrence as long as they meet the following criteria: - Surgical resection of all possible sites of suspected pulmonary metastases in order to achieve a complete remission within 4 weeks prior to study enrollment** - Pathologic confirmation of metastases from at least one of the resected sites - For patients with bilateral pulmonary metastases, resection must be performed from both lungs and the study enrollment must be within 4 weeks from date of the last lung surgery - Note: If surgery related changes such as atelectasis are seen on the post-operative computed tomography (CT) scan, patients will remain eligible to enroll as long as the operating surgeon believes that all sites of metastases were resected; patients with positive microscopic margins will be eligible to enroll - Patient must have adequate 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 anti-cancer therapy: must not have been received within 2 weeks of study entry (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 radiation therapy (RT) (small port); >= 6 weeks 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 - Surgery: >= 2 weeks from last major surgery, including pulmonary metastasectomy, with the exclusion of a central line placement and core needle or small open biopsies - Patient must not have received pegfilgrastim within 14 days of enrollment - Patient must not have received filgrastim (G-CSF, Neupogen) within 7 days of enrollment - Patient must not have received immune suppressants: corticosteroids (for other than allergic reactions and anaphylaxis), cyclosporine or tacrolimus within 7 days of enrollment - Note: the use of topical and/or inhalational steroids is allowed - Total absolute phagocyte count (APC = [%neutrophils + %monocytes) x white blood cells [WBC]) is at least 1000/uL - Platelet count >= 50,000/uL - 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: - 1 month to < 6 months: 0.4 (male) 0.4 (female) - 6 months to < 1 year: 0.5 (male), 0.5 (female) - 1 to < 2 years: 0.6 (male), 0.6 (female) - 2 to < 6 years: 0.8 (male), 0.8 (female) - 6 to < 10 years: 1 (male), 1 (female) - 10 to < 13 years: 1.2 (male), 1.2 (female) - 13 to < 16 years: 1.5 (male), 1.4 (female) - >= 16 years: 1.7 (male), 1.4 (female) - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L) - Serum albumin >= 2 g/dL - Baseline electrocardiogram (EKG) shows normal corrected QT interval (QTc) interval of =< 470 milliseconds (ms) - Shortening fraction of >= 27% by echocardiogram, or - Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram - No evidence of dyspnea at rest, no history of exercise intolerance, and a pulse oximetry > 94% - Patient has no known history of seizure disorder - Central nervous system (CNS) toxicity including peripheral neuropathy =< grade 2 Exclusion Criteria: - Patients with distant bone metastases at original diagnosis or relapse (patients with only skip lesions will be eligible) - Patients with concurrent local and pulmonary recurrence at the time of enrollment; note: patients who had local recurrence previously that has been treated and now present with an isolated pulmonary recurrence and meet the surgical resection criteria stated above will be eligible - Patients with primary refractory disease with progression of the primary tumor on initial therapy - Patients with CNS disease or other sites of extra-pulmonary metastases at the time of most recent episode of disease recurrence preceding enrollment - Patients with a prior hypersensitivity reaction to sargramostim - Patients who have received prior anti-GD2 therapy, including chimeric antigen receptor (CAR) T cells directed against GD2 antigen - 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; patients should maintain adequate contraception for a minimum of 2 months after the last dose of ch14.18 (dinutuximab)

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Dinutuximab
Given IV
Other:
Laboratory Biomarker Analysis
Correlative studies
Pharmacological Study
Correlative studies
Biological:
Sargramostim
Given SC

Locations

Country Name City State
Australia Monash Medical Center-Clayton Campus Clayton Victoria
Australia John Hunter Children's Hospital Hunter Regional Mail Centre New South Wales
Australia Women's and Children's Hospital-Adelaide North Adelaide South Australia
Australia Royal Children's Hospital Parkville Victoria
Australia Princess Margaret Hospital for Children Perth Western Australia
Australia Sydney Children's Hospital Randwick New South Wales
Australia Queensland Children's Hospital South Brisbane Queensland
Australia The Children's Hospital at Westmead Westmead New South Wales
Canada Alberta Children's Hospital Calgary Alberta
Canada IWK Health Centre Halifax Nova Scotia
Canada Children's Hospital London Ontario
Canada Centre Hospitalier Universitaire Sainte-Justine Montreal Quebec
Canada The Montreal Children's Hospital of the MUHC Montreal Quebec
Canada CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL) Quebec
Canada Hospital for Sick Children Toronto Ontario
Canada CancerCare Manitoba Winnipeg Manitoba
New Zealand Christchurch Hospital Christchurch
New Zealand Starship Children's Hospital Grafton Auckland
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 C S Mott Children's Hospital Ann Arbor Michigan
United States Children's Healthcare of Atlanta - Egleston Atlanta Georgia
United States Children's Hospital Colorado Aurora Colorado
United States Dell Children's Medical Center of Central Texas Austin Texas
United States Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland
United States Sinai Hospital of Baltimore Baltimore Maryland
United States Eastern Maine Medical Center Bangor Maine
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 Montefiore Medical Center - Moses Campus Bronx New York
United States University of Vermont and State Agricultural College Burlington Vermont
United States Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina
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 Nationwide Children's Hospital Columbus Ohio
United States Driscoll Children's Hospital Corpus Christi Texas
United States Medical City Dallas Hospital Dallas Texas
United States UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas
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 Blank Children's Hospital Des Moines Iowa
United States Ascension Saint John Hospital Detroit Michigan
United States Kaiser Permanente Downey Medical Center Downey California
United States Duke University Medical Center Durham North Carolina
United States Sanford Broadway Medical Center Fargo North Dakota
United States Cook Children's Medical Center Fort Worth Texas
United States University of Florida Health Science Center - Gainesville Gainesville Florida
United States Helen DeVos Children's Hospital at Spectrum Health Grand Rapids Michigan
United States BI-LO Charities Children's Cancer Center Greenville South Carolina
United States Hackensack University Medical Center Hackensack New Jersey
United States Connecticut Children's Medical Center Hartford Connecticut
United States Kapiolani Medical Center for Women and Children Honolulu Hawaii
United States Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas
United States Ascension Saint Vincent Indianapolis Hospital Indianapolis Indiana
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 Bronson Methodist Hospital Kalamazoo Michigan
United States Children's Mercy Hospitals and Clinics Kansas City Missouri
United States Alliance for Childhood Diseases/Cure 4 the Kids Foundation Las Vegas Nevada
United States Summerlin Hospital Medical Center Las Vegas Nevada
United States Sunrise Hospital and Medical Center Las Vegas Nevada
United States University Medical Center of Southern Nevada Las Vegas Nevada
United States Dartmouth Hitchcock Medical Center/Dartmouth Cancer 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 Norton Children's Hospital Louisville Kentucky
United States Covenant Children's Hospital Lubbock Texas
United States Valley Children's Hospital Madera California
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 Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis Minnesota
United States University of Minnesota/Masonic Cancer Center Minneapolis Minnesota
United States West Virginia University Healthcare Morgantown West Virginia
United States The Children's Hospital at TriStar Centennial Nashville Tennessee
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 Kaiser Permanente-Oakland Oakland California
United States UCSF Benioff Children's Hospital Oakland Oakland California
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
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 Arnold Palmer Hospital for Children 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 Phoenix Childrens Hospital Phoenix Arizona
United States Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania
United States Oregon Health and Science University Portland Oregon
United States Mayo Clinic in Rochester Rochester Minnesota
United States University of Rochester Rochester New York
United States Beaumont Children's Hospital-Royal Oak Royal Oak Michigan
United States University of California Davis Comprehensive Cancer Center Sacramento California
United States Cardinal Glennon Children's Medical Center Saint Louis Missouri
United States Mercy Hospital Saint Louis 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 Primary Children's Hospital Salt Lake City Utah
United States Children's Hospital of San Antonio San Antonio Texas
United States University of Texas Health Science Center at San Antonio San Antonio Texas
United States UCSF Medical Center-Mission Bay San Francisco California
United States Memorial Health University Medical Center Savannah Georgia
United States Seattle Children's Hospital Seattle Washington
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 Southern Illinois University School of Medicine Springfield Illinois
United States State University of New York Upstate Medical University Syracuse New York
United States Madigan Army Medical Center Tacoma Washington
United States Saint Joseph's Hospital/Children's Hospital-Tampa Tampa Florida
United States ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital Toledo Ohio
United States New York Medical College Valhalla New York
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,  Australia,  Canada,  New Zealand,  Puerto Rico, 

Outcome

Type Measure Description Time frame Safety issue
Other Tumor GD2 Expression Archival tumor tissue will be assessed by immunohistochemistry to provide the level of GD2 expression in tissue as an integer between 0 and 3 with 0 indicating no GD2 expression and 3 indicating strong GD2 expression. At study enrollment
Other KIR Genotype Analyses KIR mismatch will be assessed from the pre-treatment blood specimen as present or absent. At enrollment
Other NKp30c Genotype Analyses Status of the immunosuppressive isoform of NKp30c KIR mismatch will be assessed from the pre-treatment blood specimen as present or absent. At enrollment
Other FcgammaR Genotype Analyses FcgammaR genotype will be assessed from the pre-treatment blood specimen as H/R, R/R or H/H. At enrollment
Other Change in Circulating Ligand B7-H6 Levels The change in surface expression of ligand B7-H6 in terms of counts between the blood sample taken prior to the start of protocol therapy and the end of cycle 1 will be calculated. Patients who do not receive all prescribed protocol therapy during cycle 1 will not be evaluable for this outcome measure. Cycle 1 of therapy planned to be 21 days
Other Banking of Tumor Samples (Optional) Individual statistical plans will be developed for future studies answering a specific question using these banked tumor specimens. 5 cycles of protocol therapy planned as 140 days
Other HACA Titer HACA titer will be determined in each blood sample provided to the HACA reference laboratory. At enrollment, at the start of each cycle of therapy and within 30 days of the end of cycle 5
Other Circulating Tumor Deoxyribonucleic Acid Detection Statistical considerations for specific future studies will be provided. 5 cycles of protocol therapy planned as 140 days
Primary Disease Control Patients who can be confirmed to be free of detectable disease 12 months after enrollment, without intervening disease progression, will be considered to have demonstrated 12 month disease control. All other eligible patients will be considered not to have demonstrated 12 month disease control. 12 months after study enrollment
Secondary T 1/2 Alpha of the Serum Concentration of Dinutuximab T 1/2 alpha of the serum concentration of dinutuximab in days Cycle 1 Day 4 and Day 7: pre-infusion, hour 4-6, end of infusion, 4-8 hours post infusion. Once between days 11-17. Cycle 2 Day 0 or 1
Secondary T 1/2 Beta of the Serum Concentration of Dinutuximab T 1/2 beta of the serum concentration of dinutuximab in days Cycle 1 Day 4 and Day 7: pre-infusion, hour 4-6, end of infusion, 4-8 hours post infusion. Once between days 11-17. Cycle 2 Day 0 or 1
Secondary Maximum of Concentration (Cmax) of the Serum Concentration Dinutuximab Cmax of the serum concentration dinutuximab as mg/L. Cycle 1 Day 4 and Day 7: pre-infusion, hour 4-6, end of infusion, 4-8 hours post infusion. Once between days 11-17. Cycle 2 Day 0 or 1
Secondary Area Under the Curve (AUC)0 to Infinity of Serum Dinutuximab (AUC)0 to infinity of serum dinutuximab in mg-h/L. Cycle 1 Day 4 and Day 7: pre-infusion, hour 4-6, end of infusion, 4-8 hours post infusion. Once between days 11-17. Cycle 2 Day 0 or 1
Secondary Number of Cycles Where an Unacceptable Toxicity as Defined in the Protocol Using The National Cancer Institute Common Terminology Criteria for Adverse Events Version 4 Was Observed The number of cycles where a dose-limiting toxicity was identified where dose-limiting toxicity is defined in the protocol using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Occurrence of unacceptable toxicity as graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0, coded as present or absent, in each cycle received by eligible patients where all prescribed therapy for the cycle is received or the patient experiences unacceptable toxicity. 5 cycles of protocol therapy planned as 140 days
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