Denosumab in Treating Patients With Recurrent or Refractory Osteosarcoma
Condition: Metastatic Osteosarcoma; Recurrent Osteosarcoma; Refractory Osteosarcoma; Stage IV Osteosarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7
MeSH terms: Osteosarcoma; Recurrence
Intervention: Denosumab; Laboratory Biomarker Analysis; Pharmacological Study
Intervention description: Given SC; Correlative studies; Correlative studies
Intervention MeSH terms: Denosumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 11 Years
Maximum age: 49 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well denosumab works in treating patients with osteosarcoma
      that has come back (recurrent) or does not respond to treatment (refractory). Immunotherapy
      with monoclonal antibodies, such as denosumab, may help the body's immune system attack the
      cancer, and may interfere with the ability of tumor cells to grow and spread.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female patients must have a bone age of equal to or greater than 12 years of age as
             determined by local read of appropriate radiographic imaging

          -  Male patients must have a bone age of equal to or greater than 14 years of age as
             determined by local read of appropriate radiographic imaging

          -  Patients must have relapsed or become refractory to conventional therapy, with a
             regimen including some combination of high dose methotrexate, doxorubicin, cisplatin,
             ifosfamide and etoposide; and have had histologic verification of osteosarcoma at
             original diagnosis or at the time of recurrence

          -  Cohort 1 patients must have measurable disease according to Response Evaluation
             Criteria in Solid Tumors (RECIST) 1.1

          -  Cohort 2 patients must have had a complete resection of all sites of metastatic
             disease within 30 days prior to enrollment

               -  Patients will only be eligible after they have undergone complete surgical
                  resection of suspected metastatic disease that is histopathologically confirmed
                  to be osteosarcoma prior to enrollment

                    -  Note: the definition of complete resections is: gross resection of all
                       disease as per the operating surgeon; post-operative imaging is not required
                       for confirmation of complete resection

               -  Patients must undergo resection of any lung lesion meeting criteria for likely
                  metastatic disease, defined as:

                    -  3 or more lesions > 5 mm in diameter OR a single lesion > 1 cm

               -  Patients with lung as the only site of resected metastatic disease must have
                  refused participation in protocol AOST1421

                    -  Note: This applies if AOST1421 is open to enrollment at the enrolling
                       institution on the day the patient consents

          -  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

          -  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:

               -  Age: 11 to < 13 years old; 1.2 (male, female) maximum serum creatinine (mg/dL)

               -  Age: 13 to < 16 years old; 1.5 (male), 1.4 (female) maximum serum creatinine
                  (mg/dL)

               -  Age: >= 16 years old; 1.7 (male), 1.4 (female) maximum serum creatinine (mg/dL)

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
             serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
             ULN for age

          -  Serum calcium or albumin-adjusted serum calcium >= 2.0 mmol/L (8.0 mg/dL) and =< 2.9
             mmol/L (11.5 mg/dL)

        Exclusion Criteria:

          -  Patients with known sensitivity to any of the products to be administered during the
             study (eg, mammalian derived products, calcium or vitamin D)

          -  Patients who are receiving other cancer directed therapy at the time of enrollment

          -  Patients who have previously received denosumab

          -  Patients who have previously received mithramycin, strontium-89, samarium-153 or
             rhenium

          -  Patients receiving bisphosphonates

          -  Pre-existing conditions

               -  Disorders associated with abnormal bone metabolism

               -  Hypocalcemia that is not corrected with oral calcium supplementation

               -  Vitamin D < 20 mg/mL

               -  Paget's disease

               -  Prior history or current evidence of osteonecrosis of the jaw

               -  Any dental or oral condition likely to result in disruption of mucosal integrity
                  during denosumab therapy including: active dental or jaw condition requiring oral
                  surgery or tooth extraction; non-healed dental or oral surgery or planned
                  invasive dental procedures during the anticipated course of study therapy

               -  Unstable systemic disease, excluding osteosarcoma, such as unstable proximal
                  renal tubule dysfunction (Fanconi syndrome) or congestive heart failure

          -  Pregnancy and breast feeding

               -  Female patients who are pregnant; a pregnancy test is required for female
                  patients of childbearing potential

               -  Lactating females who plan to breastfeed their infants while on study therapy and
                  through 5 months after completion of study therapy

               -  Sexually active patients of reproductive potential who have not agreed to use an
                  effective contraceptive method for the duration of their study participation and
                  for 5 months after the end of study treatment

          -  All patients and/or their parents or legal guardians must sign a written informed
             consent

          -  All institutional, Food and Drug Administration (FDA), and National Cancer Institute
             (NCI) requirements for human studies must be met