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CancerPhase 2NCT00680992

Study of Denosumab in Subjects With Giant Cell Tumor of Bone

A Phase 2 study testing Denosumab in people with Cancer and Giant Cell Tumors, run by Amgen at 33 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

To determine how safe denosumab is in treating subjects with giant cell tumor of bone (GCTB) Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
Denosumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
535 participants
Where
33 sitesin 12 countries
Study dates
9 Sep 2008to 17 May 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 16Show fewer
  • 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

Trial locations and contacts

33 sites in 12 countries.

33 sites in 12 countries

United States11 sites
  • Research Site

    Ann Arbor, Michigan, 48109

  • Research Site

    Boston, Massachusetts, 02114

  • Research Site

    Boston, Massachusetts, 02215

  • Research Site

    Gainesville, Florida, 32607

  • Research Site

    Greenville, South Carolina, 29605

  • Research Site

    Minneapolis, Minnesota, 55455

  • Research Site

    New York, New York, 10003

  • Research Site

    Philadelphia, Pennsylvania, 19106

  • Research Site

    Santa Monica, California, 90403

  • Research Site

    Stanford, California, 94305

  • Research Site

    Washington D.C., District of Columbia, 20010

Other trials in United States

Australia4 sites
  • Research Site

    Camperdown, New South Wales, 2250

  • Research Site

    East Melbourne, Victoria, 3002

  • Research Site

    Nedlands, Western Australia, 6009

  • Research Site

    Woolloongabba, Queensland, 4102

Other trials in Australia

France3 sites
  • Research Site

    Lyon, 69373

  • Research Site

    Marseille, 13385

  • Research Site

    Villejuif, 94805

Other trials in France

Spain3 sites
  • Research Site

    Barcelona, Catalonia, 08025

  • Research Site

    Palma de Mallorca, Balearic Islands, 07010

  • Research Site

    Valencia, Valencia, 46026

Other trials in Spain

Canada2 sites
  • Research Site

    Montreal, Quebec, H4A 3J1

  • Research Site

    Toronto, Ontario, M5G 1X5

Other trials in Canada

Germany2 sites
  • Research Site

    Bad Saarow, 15526

  • Research Site

    Stuttgart, 70174

Other trials in Germany

Italy2 sites
  • Research Site

    Bologna, 40136

  • Research Site

    Milan, 20133

Other trials in Italy

Poland2 sites
  • Research Site

    Warsaw, 01-211

  • Research Site

    Warsaw, 02-781

Other trials in Poland

Austria1 site
  • Research Site

    Vienna, 1090

Other trials in Austria

Netherlands1 site
  • Research Site

    Leiden, 2333 ZA

Other trials in Netherlands

Sweden1 site
  • Research Site

    Lund, 221 85

Other trials in Sweden

United Kingdom1 site
  • Research Site

    Birmingham, B31 2AP

Other trials in United Kingdom

About this study

Official title: An Open-label, Multi-center, Phase 2 Study of Denosumab in Subjects With Giant Cell Tumor of Bone

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

Read the detailed description

To determine how safe denosumab is in treating subjects with GCTB

Being tested
Denosumab
Keywords
Giant Cell Tumor of Bone
Medical subject headings
Neoplasms, Giant Cell Tumors, Giant Cell Tumor of Bone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DenosumabDrug

    Also called AMG 162, Immunoglobulin G2 human monoclonal antibody to RANK ligand

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

Study groups in NCT00680992
Study groupRoleWhat they receive
DenosumabExperimental120 mg administered subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study days 8 and 15.
Receives: Drug: Denosumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

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

  2. 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.

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

    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.

    Measured: 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).

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

    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.

    Measured: At month 6.

  3. Mean Serum Denosumab Trough Concentrations

    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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 May 2008 (estimated)
  2. Study start9 Sep 2008
  3. Primary completion17 May 2018
  4. Study completion17 May 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
535 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00680992
Sponsor's protocol ID
20062004
Status last verified
Sep 2022
First submitted
15 May 2008
Last updated
22 Sep 2022

Publications

  • 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.

    PubMed 23867211
  • 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.

    PubMed 24834795
  • 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.

    PubMed 26033180
  • 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.

    PubMed 31704134
  • 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.

    PubMed 30231890
  • 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.

    PubMed 33038190
  • 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.

    PubMed 33482769
  • 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.

    PubMed 29211870
  • 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.

    PubMed 25684041

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Denosumab in people with Cancer and Giant Cell Tumors, run by Amgen at 33 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United States, Australia, France, Spain, Canada and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00680992, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2022.

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