Reduced dose-density of denosumab for maintenance therapy of unresectable giant cell tumor of bone: a multicenter phase II study "REDUCE"

* Histologically proven primary or metastatic unresectab~e 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
* 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.
* ECOGNVHO PS 0-2
* Albumin-adjusted serum calcium level >_ 2.0 mmollL (8.0 mg/d L)
* 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 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.

het Engels
* 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 &It; 30 mL/min
* Hemoglobin &It; 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
registrationKnown 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.