Bone Giant Cell Tumor
Conditions
Keywords
denosumab, Giant cell tumor of bone
Brief 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.
Interventions
Denosumab 120 mg, SC, on day 1 of every 12-week cycle
Sponsors
Amgen
European Organisation for Research and Treatment of Cancer - EORTC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | 5.8 years after first patient in | according to RECIST 1.1 |
| Osteonecrosis of the jaw (ONJ) incidence | 5.8 years after first patient in | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 5.8 years after first patient in | — |
| Denosumab treatment duration | 5.8 years after first patient in | — |
| Occurrence of Adverse Events | 5.8 years after first patient in | according to CTCAE v5.0 |
Countries
Italy, Netherlands, Spain, United Kingdom
Outcome results
None listed