Dinutuximab in Combination With Sargramostim in Treating Patients With Recurrent Osteosarcoma


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Trial ID: NCT02484443


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.

Official Title

A Phase 2 Study of Human-Mouse Chimeric Anti-disialoganglioside Monoclonal Antibody ch14.18 (Dinutuximab, NSC# 764038) in Combination With Sargramostim (GM-CSF) in Patients With Recurrent Osteosarcoma

Stanford Investigator(s)


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

      - 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

   - 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

   - Patient must not have received pegfilgrastim within 14 days of enrollment

   - Patient must not have received filgrastim (G-CSF, Neupogen) within 7 days of

   - Patient must not have received immune suppressants: corticosteroids (for other than
   allergic reactions and anaphylaxis), cyclosporine or tacrolimus within 7 days of

      - 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

   - 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)


biological: Dinutuximab

other: Laboratory Biomarker Analysis

other: Pharmacological Study

biological: Sargramostim


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Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Neyssa M. Marina