Clinical trial NCT00680992: Study of Denosumab in Subjects With Giant Cell Tumor of Bone
Official title: An Open-label, Multi-center, Phase 2 Study of Denosumab in Subjects With Giant Cell Tumor of Bone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer
Giant Cell Tumors
Giant Cell Tumor of Bone
Benign Giant Cell Tumors
Keywords: Giant Cell Tumor of Bone
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2008-05-20
Enrollment: 535
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Eligibility 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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to last study visit for treatment-emergent period (a maximum of approximately 111 months).
measure: Number of Participants Who Experienced the Maximum Toxicity Grade (CTCAE Grade ≥ 3) in the Indicated Clinical Chemistry Parameters
timeFrame: 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).
Secondary outcomes:
measure: Time to Disease Progression or Recurrence During the On-Study Period for Cohort 1, Presented as Kaplan-Meier Estimates of Probability
timeFrame: 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).
measure: Percentage of Participants Without Any On-Study Surgery at Month 6 for Cohort 2
timeFrame: At month 6.
measure: Mean Serum Denosumab Trough Concentrations
timeFrame: Blood samples were collected at baseline (day 1), days 8 and 15 and weeks 5, 9, 13 and 25.
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Research Site
state: California
city: Stanford
country: United States
facility: Research Site
state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Gainesville
country: United States
facility: Research Site
state: Florida
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: New York
country: United States
facility: Research Site
state: New York
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Camperdown
country: Australia
facility: Research Site
state: New South Wales
city: Woolloongabba
country: Australia
facility: Research Site
state: Queensland
city: East Melbourne
country: Australia
facility: Research Site
state: Victoria
city: Nedlands
country: Australia
facility: Research Site
state: Western Australia
city: Wien
country: Austria
facility: Research Site
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Lyon cedex 8
country: France
facility: Research Site
city: Marseille cedex 05
country: France
facility: Research Site
city: Villejuif cedex
country: France
facility: Research Site
city: Bad Saarow
country: Germany
facility: Research Site
city: Stuttgart
country: Germany
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Leiden
country: Netherlands
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Palma de Mallorca
country: Spain
facility: Research Site
state: Baleares
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Lund
country: Sweden
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Chawla S, Henshaw R, Seeger L, Choy E, Blay JY, Ferrari S, Kroep J, Grimer R, Reichardt P, Rutkowski P, Schuetze S, Skubitz K, Staddon A, Thomas D, Qian Y, Jacobs I. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol. 2013 Aug;14(9):901-8. doi: 10.1016/S1470-2045(13)70277-8. Epub 2013 Jul 16.
citation: Martin-Broto J, Cleeland CS, Glare PA, Engellau J, Skubitz KM, Blum RH, Ganjoo KN, Staddon A, Dominkus M, Feng A, Qian Y, Braun A, Jacobs I, Chung K, Atchison C. Effects of denosumab on pain and analgesic use in giant cell tumor of bone: interim results from a phase II study. Acta Oncol. 2014 Sep;53(9):1173-9. doi: 10.3109/0284186X.2014.910313. Epub 2014 May 19.
citation: Rutkowski P, Ferrari S, Grimer RJ, Stalley PD, Dijkstra SP, Pienkowski A, Vaz G, Wunder JS, Seeger LL, Feng A, Roberts ZJ, Bach BA. Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumor of bone. Ann Surg Oncol. 2015 Sep;22(9):2860-8. doi: 10.1245/s10434-015-4634-9. Epub 2015 Jun 2.
citation: Chawla S, Blay JY, Rutkowski P, Le Cesne A, Reichardt P, Gelderblom H, Grimer RJ, Choy E, Skubitz K, Seeger L, Schuetze SM, Henshaw R, Dai T, Jandial D, Palmerini E. Denosumab in patients with giant-cell tumour of bone: a multicentre, open-label, phase 2 study. Lancet Oncol. 2019 Dec;20(12):1719-1729. doi: 10.1016/S1470-2045(19)30663-1. Epub 2019 Nov 6.
citation: Engellau J, Seeger L, Grimer R, Henshaw R, Gelderblom H, Choy E, Chawla S, Reichardt P, O'Neal M, Feng A, Jacobs I, Roberts ZJ, Braun A, Bach BA. Assessment of denosumab treatment effects and imaging response in patients with giant cell tumor of bone. World J Surg Oncol. 2018 Sep 19;16(1):191. doi: 10.1186/s12957-018-1478-3.
citation: Bukata SV, Blay JY, Rutkowski P, Skubitz K, Henshaw R, Seeger L, Dai T, Jandial D, Chawla S. Denosumab Treatment for Giant Cell Tumor of the Spine Including the Sacrum. Spine (Phila Pa 1976). 2021 Mar 1;46(5):277-284. doi: 10.1097/BRS.0000000000003728.
citation: Palmerini E, Seeger LL, Gambarotti M, Righi A, Reichardt P, Bukata S, Blay JY, Dai T, Jandial D, Picci P. Malignancy in giant cell tumor of bone: analysis of an open-label phase 2 study of denosumab. BMC Cancer. 2021 Jan 22;21(1):89. doi: 10.1186/s12885-020-07739-8.
citation: Uday S, Gaston CL, Rogers L, Parry M, Joffe J, Pearson J, Sutton D, Grimer R, Hogler W. Osteonecrosis of the Jaw and Rebound Hypercalcemia in Young People Treated With Denosumab for Giant Cell Tumor of Bone. J Clin Endocrinol Metab. 2018 Feb 1;103(2):596-603. doi: 10.1210/jc.2017-02025.
citation: van der Heijden L, van de Sande MA, Hogendoorn PC, Gelderblom H, Dijkstra PD. Neoadjuvant denosumab for extensive giant cell tumor in os ischium: a case report. Acta Orthop. 2015 Jun;86(3):393-5. doi: 10.3109/17453674.2014.1002345. Epub 2015 Feb 14. No abstract available.