Clinical Drug Experience Knowledgebase

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.