Bone Giant Cell Tumor Clinical Trial
— REDUCEOfficial title:
Reduced Dose-density of Denosumab for Maintenance Therapy of Unresectable Giant Cell Tumor of Bone: a Multicenter Phase II Study "REDUCE"
| Verified date | January 2021 |
| Source | European Organisation for Research and Treatment of Cancer - EORTC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 2 |
| Est. completion date | July 30, 2020 |
| Est. primary completion date | July 30, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Italy | IRCCS Istituto Ortopedico Rizzoli | Bologna | |
| Netherlands | Leiden University Medical Centre | Leiden | |
| Spain | Hospital De La Santa Creu I Sant Pau | Barcelona | |
| Spain | Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia) | Barcelona | |
| Spain | Vall d'Hebron Institut d'Oncologia | Barcelona | |
| Spain | Hospital Universitario San Carlos | Madrid | |
| United Kingdom | University College London Hospitals NHS Foundation Trust - University College Hospital | London | |
| United Kingdom | Oxford University Hospitals NHS Trust - Churchill Hospital | Oxford |
| Lead Sponsor | Collaborator |
|---|---|
| European Organisation for Research and Treatment of Cancer - EORTC | Amgen |
Italy, Netherlands, Spain, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Progression free survival (PFS) | according to RECIST 1.1 | 5.8 years after first patient in | |
| Primary | Osteonecrosis of the jaw (ONJ) incidence | 5.8 years after first patient in | ||
| Secondary | Overall survival | 5.8 years after first patient in | ||
| Secondary | Denosumab treatment duration | 5.8 years after first patient in | ||
| Secondary | Occurrence of Adverse Events | according to CTCAE v5.0 | 5.8 years after first patient in |