Neoplasms

Musculoskeletal Diseases

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Bone Neoplasms

Giant Cell Tumors

Giant Cell Tumor of Bone

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Bone Diseases

Neoplasms, Bone Tissue

All Drugs and Chemicals

Bone Density Conservation Agents

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulin G

Denosumab

Immunoglobulins, Intravenous

Immunologic Factors

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

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

To determine how safe denosumab is in treating subjects with GCTB

Study of Denosumab in Subjects With Giant Cell Tumor of Bone

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

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).

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.

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.

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.

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.

Amgen

Data are presented for the entire study duration and include AEs occurring during the treatment-emergent period (comprising both the initial treatment phase and retreatment phase) and AEs occurring after the treatment-emergent period (ie, during the safety follow-up phase).

All participants received denosumab 120 mg SC Q4W, starting on study day 1, with loading doses of 120 mg SC on days 8 and 15 in the first month of treatment for those enrolled in cohorts 1 or 2.

Denosumab 120 mg Q4W (All Cohorts)

Participants with surgically unsalvageable disease (eg, sacral, spinal GCTB, or multiple lesions including pulmonary metastases) were enrolled into cohort 1 and received denosumab 120 mg SC once Q4W, starting on study day 1, plus loading doses of 120 mg SC on days 8 and 15 in the first month of treatment.

Cohort 1 (Denosumab 120 mg Q4W)

Participants with surgically salvageable disease whose planned initial on-study surgery was associated with severe morbidity (eg, joint resection, limb amputation, or hemipelvectomy) were enrolled into cohort 2 and received denosumab 120 mg SC Q4W, starting on study day 1, plus loading doses of 120 mg SC on days 8 and 15 in the first month of treatment.

Cohort 2 (Denosumab 120 mg Q4W)

Participants who participated in study 20040215 and were eligible to enroll in the current study (20062004) for continuation of treatment were enrolled into cohort 3 and received denosumab 120 mg SC Q4W, starting on study day 1. Participants in cohort 3 did not receive loading doses of denosumab on days 8 and 15 in the first month of treatment.

Cohort 3 (Denosumab 120 mg Q4W)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

White or Caucasian

Black or African American

Hispanic or Latino

Asian

Native Hawaiian or Other Pacific Islander

Other

Race/Ethnicity, Customized

Primary resectable

Primary unresectable

Recurrent resectable

Recurrent unresectable

GCTB Disease Type

The overall baseline population consisted of the 532 participants enrolled into the treatment phase of the study.

Study Director

Any TEAE

Serious TEAE

Fatal TEAE

TEAE leading to treatment phase discontinuation

TEAE leading to study drug discontinuation

CTCAE Grade 3, 4, or 5

Any TEAE related to study drug

The safety analysis set included all enrolled participants who received at least one dose of denosumab on the study.

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

Calcium corrected Grade 3 (Above)

Calcium corrected Grade 4 (Above)

Calcium corrected Grade 3 (Below)

Calcium corrected Grade 4 (Below)

Phosphate Grade 3 (Below)

Magnesium Grade 3 (Above)

Magnesium Grade 3 (Below)

Creatinine Grade 3 (Above)

Albumin Grade 3 (Below)

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

Month 6

Month 12

Month 24

Month 36

Month 60

The efficacy analysis set included all enrolled participants who were eligible for the study, and who received at least one dose of denosumab on the study. Analysis was performed on cohort 1 only.

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

The efficacy analysis set included all enrolled participants who were eligible for the study, and who received at least one dose of denosumab on the study. Analysis was performed on cohort 2 only for those who had the opportunity to be on-study for at least 6 months.

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

Day 1

Day 8

Day 15

Week 5

Week 9

Week 13

Week 17

Week 25

Adolescent participants enrolled in the PK substudy who received at least 1 dose of denosumab with baseline PK measurement and at least 1 post-baseline PK measurement were included in the adolescent PK analysis set. Participants received denosumab 120 mg SC Q4W, starting on study day 1, with loading doses of 120 mg SC on days 8 and 15 in the first month of treatment for those enrolled in cohorts 1 or 2.

Adolescent PK Subset (Denosumab 120 mg Q4W)

Adult participants enrolled in the PK substudy who received at least 1 dose of denosumab with baseline PK measurement and at least 1 post-baseline PK measurement were included in the adult PK analysis set. Participants received denosumab 120 mg SC Q4W, starting on study day 1, with loading doses of 120 mg SC on days 8 and 15 in the first month of treatment for those enrolled in cohorts 1 or 2.

Adult PK Subset (Denosumab 120 mg Q4W)

The PK analysis set included all participants who received at least 1 dose of denosumab with baseline PK measurement and at least 1 post-baseline PK measurement. Only participants with available data at each time point were included in the analysis.

Mean Serum Denosumab Trough Concentrations

Participants with surgically unsalvageable disease (eg, sacral, spinal giant cell tumor of bone (GCTB), or multiple lesions including pulmonary metastases) were enrolled into cohort 1 and received denosumab 120 milligrams (mg) subcutaneously (SC) once every 4 weeks (Q4W), starting on study day 1, plus loading doses of 120 mg SC on days 8 and 15 in the first month of treatment.

Spots Global Cancer Trial Database for Study of Denosumab in Subjects With Giant Cell Tumor of Bone

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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