reduced dose-density of denosumab for unresectable gctb

Conditions: Bone Giant Cell Tumor

Summary: this study is a multi-center, multi-national, open label, single arm phase 2 study of single-agent denosumab. the objective of the trial is to evaluate the risk versus benefit of denosumab in maintenance setting in patients requiring long-term use (\> 1 year) of denosumab. for that purpose, the treatment schedule with reduced dose density (120mg sc 12-weekly instead of 4-weekly) will be investigated, starting after 1-year (12-15 months) of denosumab full dose, as per current label. the impact on osteonecrosis of the jaw (onj) without compromising disease control will be assessed.


Eligibility criteria:
inclusion criteria: * histologically proven primary or metastatic unresectable gctb or resectable gctb but not a candidate for surgery, excluding primary or metastatic gctb in the jaw. * evidence of active disease at time of registration based on local investigator's assessment (according to recist v1.1) * age ≥ 18 years old and skeletally mature (ie, radiographic evidence of at least 1 mature long bone (e.g. humerus with closed growth epiphyseal plate) * patient must have received denosumab before entering this trial: * the duration of treatment with full dose denosumab (120 mg sc ) as per current label must be at least 12 months and patient may have received up to 15 months of denosumab. * and patient must have received at least 12 doses of denosumab 120 mg before entering into this trial. * ecog/who ps 0-2 * albumin-adjusted serum calcium level ≥ 2.0 mmol/l (8.0 mg/dl) * representative formalin fixed, paraffin embedded tumor blocks or unstained tissue slides, either from the primary tumor or a metastatic lesion, must be available for histological central review. * women of child bearing potential (wocbp) must have a negative serum (or urine) pregnancy test within 7 days prior to the first reduced dose of study treatment. * wocbp should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 5 months after the last treatment cycle. a highly effective method of birth control is defined as a method which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. such methods include: * combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) * progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) * intrauterine device (iud) * intrauterine hormone-releasing system (ius) * bilateral tubal occlusion * vasectomized partner * sexual abstinence (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient) * female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 5 months after the last study treatment. * before patient registration, written informed consent must be given according to ich/gcp, and national/local regulations. exclusion criteria: * currently receiving other gctb specific treatment (eg, radiation, chemotherapy, or embolization) * concurrent bisphosphonate treatment and calcitonin * known or suspected current diagnosis of underlying malignancy including high-grade sarcoma, osteosarcoma, fibrosarcoma, malignant giant cell sarcoma * known diagnosis of second malignancy within the past 5 years (subjects with definitively treated basal cell carcinoma and cervical carcinoma in situ are permitted) * creatinine clearance \< 30 ml/min * hemoglobin \< 10.0 g/dl or 6.2 mmol/l * prior history or current evidence of osteonecrosis/osteomyelitis of the jaw * active dental or jaw condition which requires oral surgery, including tooth extraction * non-healed dental/oral surgery * planned invasive dental procedure for the course of the study * known hypersensitivity to the active substance or to any of the excipients (glacial acetic acid, sodium hydroxide, sorbitol (e420), polysorbate 20) * treatment with other investigational device or drug 30 days prior to registration * known hypersensitivity to products to be administered during the study (calcium and/or vitamin d) * unstable systemic disease including active and uncontrolled infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months before registration * any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Keywords: denosumab giant cell tumor of bone