Denosumab in Treating Patients With Recurrent or Refractory Osteosarcoma

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 15-008688
    NCT ID: NCT02470091
    Sponsor Protocol Number: AOST1321

About this study

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). Monoclonal antibodies, such as denosumab, may block tumor growth in different ways by targeting certain cells.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See 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
    • Note: Patients in Cohort 1 will be stratified as follows:
      • Stratum 1: Patients >= 11 years of age but < 18 years
      • Stratum 2: Patients >= 11 years of age but < 50 years
  • 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
  • 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)
  • 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

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
    • 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
    • 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
    • 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

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Carola A Arndt, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

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CLS-20169987

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