giant cell rich tumors of bone
Conditions
Interventions
Denosumab will be given in a dose of 120mg subcutaneously (SC) on day 1 of
every 4 week cycle with a loading dose of 120mg SC on days 8 and 15 of the
first cycle. Maximum treatment period is 3 years
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: The population will consist of patients with the following tumor types:;- Pathologically proven giant cell rich tumor ;* ABC;* GCG;* Other giant cell rich lesions (primary bone, non-malignant, pathology and radiology to be reviewed during multidisciplinary meeting LUMC);- Patients with surgically unsalvageable disease (e.g., sacral, spinal giant cell rich tumors, or multiple lesions including pulmonary metastases) OR patients whose planned surgery includes joint resection, limb amputation, hemipelvectomy or surgical procedure resulting in severe morbidity;- Measurable evidence of active disease within 1 year before study enrollment;- Albumin-adjusted serum calcium level * 2.0 mmol/L (8.0 mg/dL);- Aged 18 years and up and skeletally mature ;- ECOG performance status 0, 1 or 2;- Written signed informed consent
Exclusion criteria
Exclusion criteria: - Known or suspected current diagnosis of classic GCTB;- Known or suspected current diagnosis of underlying malignancy including but not limited to high-grade sarcoma, osteosarcoma, fibrosarcoma, malignant giant cell sarcoma;- Known or suspected current diagnosis of brown cell tumor of hyperparathyroidism, Paget*s disease or cherubism;- Known or suspected current diagnosis of primary soft tissue tumor with invasion of the bone ;- Known diagnosis of other malignancy within the past 5 years (patients with definitively treated basal cell carcinoma and cervical carcinoma in situ are permitted);- Previous treatment with denosumab (with the exception of patients eligible for re-treatment with denosumab after completing this study);- 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 denosumab;- Known hypersensitivity to products to be administered during the study (calcium and/or vitamin D) ;- Currently receiving other specific treatment for giant cell rich tumors of bone (e.g., radiation, chemotherapy or embolization);- Concurrent bisphosphonate treatment;- Major surgery less than 4 weeks prior to start of treatment;- Treatment with other investigational device or drug 30 days prior to study enrollment ;- Unstable systemic disease including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months before study enrollment;- Patient is pregnant or breast feeding, or planning to become pregnant within 5 months after the EOT visit;- Patient or partner of patient of child bearing potential is not willing to use a highly effective method of contraception during treatment and for 5 months after the EOT visit;- Patient has any kind of disorder that compromises the ability of the patient to give written informed consent and/or to comply with study procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Subjects with salvageable giant cell rich tumors: - The proportion of subjects who do not require surgery during the study - The proportion of subjects undergoing the planned versus performed type of surgery during the study Subjects with unsalvageable giant cell rich tumors (combined endpoint): - Disease control: o Radiological response assessed by combined RECIST, PET, inverse Choi when available AND/OR o No progression at 1 year (based on disease assessment) - Stable pain score, defined as * 1 point increase on *worst pain* question in BPI-SF | — |
Secondary
| Measure | Time frame |
|---|---|
| - Frequency of adverse events (AEs), as determined by Common Terminology Criteria for Adverse Events (CTCAE) v. 4.03 criteria - The proportion of subjects with disease recurrence after denosumab followed by surgery during the study - Symptomatic improvement in the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire C30 (EORTC QLC-30) / BPI-SF, including: 1) Change from baseline at 1 year, and 2) Time to improvement in pain and time to worsening of pain - Time to surgery (for subjects with salvageable disease), time to recurrence after surgery, progression free survival Translational research: - Translational studies. Systematic analysis of pathologic and molecular markers on tumor material, including evaluation of pathological response for subjects undergoing surgery | — |
Countries
Netherlands
Outcome results
None listed