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About
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.
Full 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.
Enrollment
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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
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
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
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:
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
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41 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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