Study of Denosumab in Subjects With Giant Cell Tumor of Bone

NCT00680992 | Completed Phase 2 Results

• 1 other identifier: 20062004
• Study Type: interventional
• Target: 535
• Locations: 11 countries
• Sites: 32

Brief Summary

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

Conditions

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

Keywords

Giant Cell Tumor of Bone

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  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).

  From first dose of study drug up to last study visit for treatment-emergent period (a maximum of approximately 111 months).

• Number of Participants Who Experienced the Maximum Toxicity Grade (CTCAE Grade ≥ 3) in the Indicated Clinical Chemistry Parameters

  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.

  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 (3)

• Time to Disease Progression or Recurrence During the On-Study Period for Cohort 1, Presented as Kaplan-Meier Estimates of Probability

  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).

• Percentage of Participants Without Any On-Study Surgery at Month 6 for Cohort 2

  At month 6.

• Mean Serum Denosumab Trough Concentrations

  Blood samples were collected at baseline (day 1), days 8 and 15 and weeks 5, 9, 13 and 25.

Study Arms (1)

Denosumab

EXPERIMENTAL

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

Interventions

Denosumab DRUG

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

Also known as: AMG 162, Immunoglobulin G2 human monoclonal antibody to RANK ligand

Denosumab

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (33)

Research Site

Santa Monica, California, 90403, United States

Location

Research Site

Stanford, California, 94305, United States

Location

Research Site

Washington D.C., District of Columbia, 20010, United States

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Gainesville, Florida, 32607, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02215, United States

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Ann Arbor, Michigan, 48109, United States

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Minneapolis, Minnesota, 55455, United States

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New York, New York, 10003, United States

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Philadelphia, Pennsylvania, 19106, United States

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Greenville, South Carolina, 29605, United States

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Camperdown, New South Wales, 2250, Australia

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Woolloongabba, Queensland, 4102, Australia

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East Melbourne, Victoria, 3002, Australia

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Nedlands, Western Australia, 6009, Australia

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Vienna, 1090, Austria

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Toronto, Ontario, M5G 1X5, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Lyon, 69373, France

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Marseille, 13385, France

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Villejuif, 94805, France

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Bad Saarow, 15526, Germany

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Stuttgart, 70174, Germany

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Bologna, 40136, Italy

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Milan, 20133, Italy

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Leiden, 2333 ZA, Netherlands

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Warsaw, 01-211, Poland

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Warsaw, 02-781, Poland

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Palma de Mallorca, Balearic Islands, 07010, Spain

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Barcelona, Catalonia, 08025, Spain

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Valencia, Valencia, 46026, Spain

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Lund, 221 85, Sweden

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Birmingham, B31 2AP, United Kingdom

Location

Related Publications (9)

• 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.

  PMID: 23867211 BACKGROUND

• 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.

  PMID: 24834795 BACKGROUND

• 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.

  PMID: 26033180 BACKGROUND

• 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.

  PMID: 31704134 BACKGROUND

• 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.

  PMID: 30231890 BACKGROUND

• 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.

  PMID: 33038190 BACKGROUND

• 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.

  PMID: 33482769 DERIVED

• 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.

  PMID: 29211870 DERIVED

• 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.

  PMID: 25684041 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Neoplasms; Giant Cell Tumors; Giant Cell Tumor of Bone

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms, Bone Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2008
• First Posted: May 20, 2008
• Study Start: September 9, 2008
• Primary Completion: May 17, 2018
• Study Completion: May 17, 2018
• Last Updated: September 22, 2022
• Results First Posted: December 10, 2018

Record last verified: 2022-09

Locations

IT (2); DE (2); ES (3); CA (2); PL (2); SE (1); US (11); NL (1); AU (4); GB (1); FR (3)