This study is a multi-center, multi-national, open label, single arm phase 2 study of
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
- 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,
- 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.
- Currently receiving other GCTB specific treatment (eg, radiation, chemotherapy, or
- 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
- 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
- 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.