Dinutuximab in Combo w/ Sargramostim for Recurrent Osteosarcoma

A Phase II Study of Human-Mouse Chimeric Anti-Disialoganglioside Monoclonal Antibody ch14.18 (Dinutuximab, NSC# 764038, IND# 4308) in Combination with Sargramostim (GM-CSF) in Patients with Recurrent Osteosarcoma

November 22, 2017

  • Clinical Trial Information

    Trial Contact: El-Shami, Jessica; Leffin, Melissa; Francois, Laetitia Claire; Spinelli, Jennifer

  • IRB No: AOST1421

    Protocol Abbrev: AOST1421

    Principal Investigator: Vincent F. Giusti, MD

    Sub Investigators: AguilarBonilla, Ana MD; Eslin, Don MD; Smith, Amy MD; Sutphin, Robert MD; Levy, Alejandro MD; Story, Allison ARNP; Pope, Michele ARNP

    Phase: Drug: Phase II

    Age Group: Pediatric

    Secondary Protocol No: AOST1421

    Treatment: Medication

    Applicable Disease Sites: Osteosarcoma

    Therapies Involved: Drug:Dinutuximab, Sargramostim

    ClinicalTrials.gov ID: NCT02484443

  • Objective

    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). Dinutuximab is a type of drug called a monoclonal antibody. It is designed to recognize a specific target on the surface of cancer cells. It then attaches to the cancer cells and kills them, without harming normal cells. Sargramostim may help the body increase the amount of white blood cells it produces, which help the body fight off infections. Giving sargramostim with dinutuximab may help the dinutuximab work better and kill more cancer cells.

  • Key Eligibility

    Eligibility
    Ages Eligible for Study: up to 29 Years
    Genders Eligible for Study: Both
    Accepts Healthy Volunteers: No

    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 (Neulasta) 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
    •  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%
    •  Patients with a known seizure disorder may be enrolled if on anticonvulsants and/or well controlled
    •  Central nervous system (CNS) toxicity including peripheral neuropathy =< grade 2