Dinutuximab in Combination With Sargramostim in Treating Patients With Recurrent Osteosarcoma
Condition: Metastatic Malignant Neoplasm in the Lung; Metastatic Osteosarcoma; Recurrent Osteosarcoma
MeSH terms: Neoplasms; Osteosarcoma; Recurrence
Intervention: Dinutuximab; Laboratory Biomarker Analysis; Pharmacological Study; Sargramostim
Intervention description: Given IV; Correlative studies; Correlative studies; Given SC
Intervention MeSH terms: Dinutuximab; Sargramostim; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Maximum age: 29 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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)