Dinutuximab in Combination With Sargramostim in Treating Patients With Recurrent Osteosarcoma

This is an interventional treatment trial for Metastatic Malignant Neoplasm in the Lung Read More

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)