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Study of Denosumab in Subjects With Giant Cell Tumor of Bone

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ClinicalTrials.gov Identifier: NCT00680992
Recruitment Status : Completed
First Posted : May 20, 2008
Results First Posted : December 10, 2018
Last Update Posted : February 19, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
To determine how safe denosumab is in treating subjects with giant cell tumor of bone (GCTB)

Condition or disease Intervention/treatment Phase
Cancer Giant Cell Tumors Giant Cell Tumor of Bone Benign Giant Cell Tumors Drug: Denosumab Phase 2

Detailed Description:
To determine how safe denosumab is in treating subjects with GCTB

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 535 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Multi-center, Phase 2 Study of Denosumab in Subjects With Giant Cell Tumor of Bone
Actual Study Start Date : September 9, 2008
Actual Primary Completion Date : May 17, 2018
Actual Study Completion Date : May 17, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bone Cancer
Drug Information available for: Denosumab

Arm Intervention/treatment
Experimental: Denosumab
120 mg administered subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study days 8 and 15.
Drug: Denosumab
120 mg administered subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study days 8 and 15.
Other Name: AMG 162, Immunoglobulin G2 human monoclonal antibody to RANK ligand




Primary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: From first dose of study drug up to last study visit for treatment-emergent period (a maximum of approximately 111 months). ]
    AE defined as any untoward medical occurrence in a clinical trial participant. Serious AE defined as AE that is fatal, life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or other significant medical hazard. Severity of AEs assessed according to Common Terminology Criteria for Adverse Events (CTCAE, v3.0) based on the general guideline: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening or disabling; Grade 5: Death related to AE. Investigator assessed AEs for relatedness to study drug. Results are presented for treatment-emergent events (TEAEs) and included all AEs occurring from first dose in initial treatment phase to end of initial treatment phase (or for participants entering retreatment, from first dose in initial treatment phase until end of retreatment phase).

  2. Number of Participants Who Experienced the Maximum Toxicity Grade (CTCAE Grade ≥ 3) in the Indicated Clinical Chemistry Parameters [ Time Frame: Baseline (day 1) up to last study visit for initial treatment phase (median duration approximately 30 months up to a maximum of approximately 109 months). ]
    Serum samples for clinical chemistry were collected on study day 1 (baseline), day 15, week 5 and each study visit Q4W thereafter until last study visit for the on-study period (ie, until end of initial treatment phase). The parameters included albumin, calcium (albumin-adjusted), creatinine, magnesium and phosphate. Results are presented for number of participants who experienced the maximum toxicity grade for each of these clinical parameters. The maximum toxicity grade experienced by each participant was based on CTCAE, v3.0, and are summarized for Grade 3 and 4. Increases and decreases in relationship to the normal parameter ranges are indicated as 'Above' and 'Below' respectively.


Secondary Outcome Measures :
  1. Time to Disease Progression or Recurrence During the On-Study Period for Cohort 1, Presented as Kaplan-Meier Estimates of Probability [ Time Frame: From first dose of study drug up to the end of the initial treatment phase (median duration approximately 30 months up to a maximum of approximately 109 months). ]
    Time to disease progression or recurrence during the on-study period was defined as the time interval (in days) from the date of first dose of study drug to the date of earliest Progressive Disease (PD) during the initial treatment phase. PD was defined as the response of progressive disease, locally recurrent disease or relapse as captured in the Disease Status page of the Case Report Form. If a participant had not had PD by the end of the initial treatment phase date, time to disease progression or recurrence were censored at her/his end of initial treatment phase date. Since median time to disease progression or recurrence for participants in cohort 1 was not reached, Kaplan-Meier estimates for the probability (expressed as a percentage) of participants in cohort 1 to have disease progression or recurrence at months 6, 12, 24, 36 and 60 are presented.

  2. Percentage of Participants Without Any On-Study Surgery at Month 6 for Cohort 2 [ Time Frame: At month 6. ]
    The percentage of participants without any surgery at month 6 was equivalent to the number of participants without any surgery by month 6 divided by the number of cohort 2 participants who had an opportunity to complete 6 months of treatment, expressed as a percentage.

  3. Mean Serum Denosumab Trough Concentrations [ Time Frame: Blood samples were collected at baseline (day 1), days 8 and 15 and weeks 5, 9, 13 and 25. ]
    Blood samples for determination of serum denosumab concentration levels were obtained from participants included in the pharmacokinetic (PK) substudy at baseline (prior to administration of study drug on day 1) and at scheduled time points during the study up to week 25.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Pathologically confirmed GCTB 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 GCTB, or multiple lesions including pulmonary metastases) OR subjects whose planned surgery includes joint resection, limb amputation, hemipelvectomy or surgical procedure resulting in severe morbidity
  • Karnofsky performance status equal or greater than 50% (ie, Eastern Cooperative Oncology Group status 0, 1, or 2)
  • Adults or skeletally mature adolescents (ie, radiographic evidence of at least 1 mature long bone [eg, humerus with closed growth epiphyseal plate]) equal or greater than 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

Exclusion criteria:

  • 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(s), 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 5 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 5 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00680992


Locations
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United States, California
Research Site
Santa Monica, California, United States, 90403
Research Site
Stanford, California, United States, 94305
United States, District of Columbia
Research Site
Washington, District of Columbia, United States, 20010
United States, Florida
Research Site
Gainesville, Florida, United States, 32607
United States, Massachusetts
Research Site
Boston, Massachusetts, United States, 02114
Research Site
Boston, Massachusetts, United States, 02215
United States, Michigan
Research Site
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Research Site
Minneapolis, Minnesota, United States, 55455
United States, New York
Research Site
New York, New York, United States, 10003
United States, Pennsylvania
Research Site
Philadelphia, Pennsylvania, United States, 19106
United States, South Carolina
Research Site
Greenville, South Carolina, United States, 29605
Australia, New South Wales
Research Site
Camperdown, New South Wales, Australia, 2250
Australia, Queensland
Research Site
Woolloongabba, Queensland, Australia, 4102
Australia, Victoria
Research Site
East Melbourne, Victoria, Australia, 3002
Australia, Western Australia
Research Site
Nedlands, Western Australia, Australia, 6009
Austria
Research Site
Wien, Austria, 1090
Canada, Ontario
Research Site
Toronto, Ontario, Canada, M5G 1X5
Canada, Quebec
Research Site
Montreal, Quebec, Canada, H4A 3J1
France
Research Site
Lyon cedex 8, France, 69373
Research Site
Marseille cedex 05, France, 13385
Research Site
Villejuif cedex, France, 94805
Germany
Research Site
Bad Saarow, Germany, 15526
Research Site
Stuttgart, Germany, 70174
Italy
Research Site
Bologna, Italy, 40136
Research Site
Milano, Italy, 20133
Netherlands
Research Site
Leiden, Netherlands, 2333 ZA
Poland
Research Site
Warszawa, Poland, 01-211
Research Site
Warszawa, Poland, 02-781
Spain
Research Site
Palma de Mallorca, Baleares, Spain, 07010
Research Site
Barcelona, Cataluña, Spain, 08025
Research Site
Valencia, Comunidad Valenciana, Spain, 46026
Sweden
Research Site
Lund, Sweden, 221 85
United Kingdom
Research Site
Birmingham, United Kingdom, B31 2AP
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
  Study Documents (Full-Text)

Documents provided by Amgen:
Study Protocol  [PDF] September 15, 2015
Statistical Analysis Plan  [PDF] July 17, 2018

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00680992    
Other Study ID Numbers: 20062004
First Posted: May 20, 2008    Key Record Dates
Results First Posted: December 10, 2018
Last Update Posted: February 19, 2019
Last Verified: February 2019
Keywords provided by Amgen:
Giant Cell Tumor of Bone
Additional relevant MeSH terms:
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Neoplasms
Giant Cell Tumors
Bone Neoplasms
Giant Cell Tumor of Bone
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms by Site
Bone Diseases
Musculoskeletal Diseases
Neoplasms, Bone Tissue
Denosumab
Immunoglobulins
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs
Bone Density Conservation Agents