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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00680992




Registration number
NCT00680992
Ethics application status
Date submitted
15/05/2008
Date registered
20/05/2008
Date last updated
19/02/2019

Titles & IDs
Public title
Study of Denosumab in Subjects With Giant Cell Tumor of Bone
Scientific title
An Open-label, Multi-center, Phase 2 Study of Denosumab in Subjects With Giant Cell Tumor of Bone
Secondary ID [1] 0 0
20062004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 0 0
Giant Cell Tumors 0 0
Giant Cell Tumor of Bone 0 0
Benign Giant Cell Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Other cancer types
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Denosumab

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.


Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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).
Timepoint [1] 0 0
From first dose of study drug up to last study visit for treatment-emergent period (a maximum of approximately 111 months).
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
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 outcome [1] 0 0
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.
Timepoint [1] 0 0
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).
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
At month 6.
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Blood samples were collected at baseline (day 1), days 8 and 15 and weeks 5, 9, 13 and 25.

Eligibility
Key inclusion 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
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Woolloongabba
Recruitment hospital [3] 0 0
Research Site - East Melbourne
Recruitment hospital [4] 0 0
Research Site - Nedlands
Recruitment postcode(s) [1] 0 0
2250 - Camperdown
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3002 - East Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
South Carolina
Country [10] 0 0
Austria
State/province [10] 0 0
Wien
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Canada
State/province [12] 0 0
Quebec
Country [13] 0 0
France
State/province [13] 0 0
Lyon cedex 8
Country [14] 0 0
France
State/province [14] 0 0
Marseille cedex 05
Country [15] 0 0
France
State/province [15] 0 0
Villejuif cedex
Country [16] 0 0
Germany
State/province [16] 0 0
Bad Saarow
Country [17] 0 0
Germany
State/province [17] 0 0
Stuttgart
Country [18] 0 0
Italy
State/province [18] 0 0
Bologna
Country [19] 0 0
Italy
State/province [19] 0 0
Milano
Country [20] 0 0
Netherlands
State/province [20] 0 0
Leiden
Country [21] 0 0
Poland
State/province [21] 0 0
Warszawa
Country [22] 0 0
Spain
State/province [22] 0 0
Baleares
Country [23] 0 0
Spain
State/province [23] 0 0
Cataluña
Country [24] 0 0
Spain
State/province [24] 0 0
Comunidad Valenciana
Country [25] 0 0
Sweden
State/province [25] 0 0
Lund
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Birmingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To determine how safe denosumab is in treating subjects with giant cell tumor of bone (GCTB)
Trial website
https://clinicaltrials.gov/show/NCT00680992
Trial related presentations / 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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications