Study of Denosumab in Subjects With Giant Cell Tumor of Bone

NCT ID: NCT00680992

Last Updated: 2022-09-22

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

535 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-09-09

Study Completion Date

2018-05-17

Brief Summary

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

Detailed Description

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To determine how safe denosumab is in treating subjects with GCTB

Conditions

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Cancer Giant Cell Tumors Giant Cell Tumor of Bone Benign Giant Cell Tumors

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Denosumab

120 mg administered subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study days 8 and 15.

Group Type EXPERIMENTAL

Denosumab

Intervention Type DRUG

120 mg administered subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study days 8 and 15.

Interventions

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Denosumab

120 mg administered subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study days 8 and 15.

Intervention Type DRUG

Other Intervention Names

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AMG 162, Immunoglobulin G2 human monoclonal antibody to RANK ligand

Eligibility Criteria

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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
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Research Site

Santa Monica, California, United States

Site Status

Research Site

Stanford, California, United States

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Washington D.C., District of Columbia, United States

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Gainesville, Florida, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Minneapolis, Minnesota, United States

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New York, New York, United States

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Philadelphia, Pennsylvania, United States

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Greenville, South Carolina, United States

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Camperdown, New South Wales, Australia

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Woolloongabba, Queensland, Australia

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East Melbourne, Victoria, Australia

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Nedlands, Western Australia, Australia

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Vienna, , Austria

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Lyon, , France

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Marseille, , France

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Villejuif, , France

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Bad Saarow, , Germany

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Stuttgart, , Germany

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Bologna, , Italy

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Milan, , Italy

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Leiden, , Netherlands

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Warsaw, , Poland

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Warsaw, , Poland

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Palma de Mallorca, Balearic Islands, Spain

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Barcelona, Catalonia, Spain

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Valencia, Valencia, Spain

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Lund, , Sweden

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Birmingham, , United Kingdom

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Countries

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United States Australia Austria Canada France Germany Italy Netherlands Poland Spain Sweden United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 23867211 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24834795 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26033180 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31704134 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30231890 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33038190 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33482769 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29211870 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25684041 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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20062004

Identifier Type: -

Identifier Source: org_study_id

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