Safety Study of Denosumab in Subjects With Recurrent or Unresectable Giant Cell Tumor of Bone
- Conditions
- Giant cell tumor of bone (GCTB)MedDRA version: 20.0Level: LLTClassification code 10005968Term: Bone giant cell tumorSystem Organ Class: 100000019081Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2008-001606-16-SE
- Lead Sponsor
- Amgen Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 530
- Pathologically confirmed giant cell tumor of bone within 1 year before study enrollment
- Measurable evidence of active disease within 1 year before study enrollment
- Subjects with surgically unsalvageable disease (eg, sacral, spinal GCT, or multiple lesions including pulmonary metastases) OR subjects whose planned initial surgery includes joint resection, limb amputation, hemipelvectomy or surgical procedure resulting in severe morbidity, other than curettage with complete resection of tumor
- Karnofsky performance status = 50% (ie, ECOG status 0, 1, or 2)
- Adults or skeletally mature adolescents (ie, radiographic evidence of at least 1 mature long bone [eg, humerous with closed growth epiphyseal plate]) = 12 years of age
- Skeletally mature adolescents must weigh at least 45 kg
- Before any study-specific procedure is performed, the appropriate written informed consent must be obtained.
Inclusion Criteria for 20040215 subjects:
- Subjects currently enrolled in study 20040215
- Before any study-specific procedure is performed, the appropriate written informed consent must be obtained
Are the trial subjects under 18? yes
Number of subjects for this age range: 28
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 479
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 23
- Currently receiving other GCTB specific treatment (eg, radiation, chemotherapy, or embolization)
- Concurrent bisphosphonate treatment
- Known or suspected current diagnosis of underlying malignancy including high-grade sarcoma, osteosarcoma, fibrosarcoma, malignant giant cell sarcoma
- Known or suspected current diagnosis of non GCTB giant cell-rich tumors
- Known or suspected current diagnosis of brown cell tumor of bone or Paget’s disease
- Known diagnosis of second malignancy within the past 5 years (subjects with definitively treated basal cell carcinoma and cervical carcinoma in situ are permitted)
- 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
- Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(ies), or subject is receiving other investigational agent(s)
- Subject has known sensitivity to any of the products to be administered during dosing
- Unstable systemic disease including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months before enrollment
- Subject is pregnant or breast feeding, or planning to become pregnant within 7 months after the end of treatment
- Female subject of child bearing potential is not willing to use two methods of highly effective contraception during treatment and for 7 months after the end of treatment
- Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
Exclusion Criteria for 20040215 subjects:
- Developed sensitivity to mammalian cell derived drug products during the 20040215 study
- Currently receiving any unapproved investigational product other than denosumab
- Subject is pregnant or breast feeding, or planning to become pregnant within 7 months after the end of treatment
- Female subject of child bearing potential is not willing to use two methods of highly effective contraception during treatment and for 7 months after the end of treatment
- Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the safety profile of denosumab in subjects with GCTB;Secondary Objective: - Evaluation of time to disease progression in subjects with unsalvageable GCTB treated with denosumab (cohort 1)<br> - Evaluation of the proportion of subjects who do not require surgery in denosumab treated subjects with salvageable GCTB (cohort 2)<br>- to evaluate denosumab pharmacokinetics (PK) in adolescent and adult subjects with GCTB (PK subset);Primary end point(s): Safety profile of denosumab characterized in terms of the type, frequency, and severity of adverse events and laboratory abnormalities for each cohort of the study.;Timepoint(s) of evaluation of this end point: Interim analyses and final analysis
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1- Time to disease progression for cohort 1<br>2- Proportion of subjects without any surgery at month 6 for cohort 2<br>3- Serum denosumab (trough) concentrations (PK subset);Timepoint(s) of evaluation of this end point: 1- Interim analyses and final analysis<br>2- Month 6<br>3- Month 6