## Protocol Section
### Identification Module
**NCT ID:** NCT00396279

**Brief Title:** Safety and Efficacy Study of Denosumab in Patients With Recurrent or Unresectable Giant Cell Tumor of Bone

**Official Title:** An Open-Label, Multi-Center, Phase 2 Safety and Efficacy Study of Denosumab (AMG 162) in Subjects With Recurrent or Unresectable Giant Cell Tumor (GCT) of Bone

#### Organization Study ID Info
**ID:** 20040215
#### Organization
**Class:** INDUSTRY
**Full Name:** Amgen
### Status Module
#### Completion Date
**Date:** 2011-02-01

**Type:** ACTUAL

#### Disp First Post Date
**Date:** 2010-06-14

**Type:** ESTIMATED

**Disp First Submit Date:** 2010-06-10
**Disp First Submit QC Date:** 2010-06-10

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-11-08

**Type:** ACTUAL

**Last Update Submit Date:** 2022-11-04

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2008-04-07

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2014-03-05

**Type:** ESTIMATED

**Results First Submit Date:** 2014-01-23

**Results First Submit QC Date:** 2014-01-23

#### Start Date
**Date:** 2006-07-10

**Type:** ACTUAL

**Status Verified Date:** 2022-11

#### Study First Post Date
**Date:** 2006-11-06
**Type:** ESTIMATED
**Study First Submit Date:** 2006-11-02
**Study First Submit QC Date:** 2006-11-02
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Amgen

#### Responsible Party

**Type:** SPONSOR

### Description Module

**Brief Summary:** To determine how safe and effective denosumab is in treating patients with giant cell tumor of bone.

### Conditions Module

**Conditions:**

- GCT

- Giant Cell Tumor of Bone

**Keywords:**

- Giant Cell Tumor of Bone

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 37

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg doses on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason.

**Intervention Names:**

- Biological: Denosumab

- Dietary Supplement: Calcium/Vitamin D

**Label:** Denosumab

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Denosumab

**Description:** Administered by subcutaneous injection

**Name:** Denosumab

**Other Names:**

- Xgeva®

**Type:** BIOLOGICAL

#### Intervention 2

**Arm Group Labels:**

- Denosumab

**Name:** Calcium/Vitamin D

**Type:** DIETARY_SUPPLEMENT

### Outcomes Module

#### Primary Outcomes

**Description:** A treatment response was defined for participants with tissue samples obtained and measured by histopathology as: • at least 90% elimination of giant cells relative to Baseline, or • complete elimination of giant cells in cases where giant cells represent \< 5% of tumor cells. A response was defined for participants who have only radiographs (histopathology not available) as lack of progression of the target lesion at week 25 by radiographic measurements compared with Baseline. For participants with both a core biopsy and resected tissue obtained, the sample closest to week 25 was used in the analysis.

**Measure:** Percentage of Participants With Giant Cell Tumor Response

**Time Frame:** From enrollment until 25 weeks

#### Secondary Outcomes

**Description:** Urinary N-telopeptide (of type 1 collagen) corrected for urine creatinine (uNTX/Cr) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in uNTX/Cr was measured over time.

**Measure:** Percent Change From Baseline in Urinary N-telopeptide Corrected for Urine Creatinine

**Time Frame:** Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81

**Description:** Serum C-terminus peptide (of type 1 collagen; CTX1) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in CTX was measured over time.

**Measure:** Percent Change From Baseline in Serum C-terminus Peptide (of Type 1 Collagen)

**Time Frame:** Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81

**Description:** Serum concentrations of denosumab were measured by a validated conventional sandwich enzyme-linked immunosorbent assay (ELISA).

**Measure:** Serum Denosumab Trough Concentrations

**Time Frame:** Blood samples were collected on Days 1 (baseline), 8, 15 and Weeks 5 (Day 29), 9, 13, 25, and 49.

**Description:** An adverse event is defined as an undesirable medical occurrence (e.g., sign, symptom, or diagnosis) or worsening of a pre-existing medical condition. A serious adverse event (SAE) is defined by regulatory authorities as one that • is fatal • is life threatening (places the participant at immediate risk of death) • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard. The severity of adverse events was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, version 3.0) based on the following general guideline: Grade 1: Mild AE Grade 2: Moderate AE Grade 3: Severe AE Grade 4: Life-threatening or disabling AE Grade 5: Death related to AE. AEs were assessed by the Investigator for relatedness to study drug.

**Measure:** Number of Participants With Adverse Events (AEs)

**Time Frame:** From the first dose of study drug until the data cut-off date of April 7 2008; a maximum of 18 months

**Description:** Validated immunoassays were used to test for the presence of anti-denosumab antibodies throughout the study.

**Measure:** Number of Participants With Anti-Denosumab Antibodies

**Time Frame:** From enrollment until the data cut-off date of April 7 2008; a maximum time of 18 months.

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Adults, 18 years and older
* Histologically confirmed and measurable giant cell tumor (GCT)
* Recurrent GCT confirmed by radiology or unresectable GCT
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

Exclusion Criteria:

* Pateints for whom surgery to the affected limb/area is planned within 27 days after receiving 1st dose of denosumab
* Radiation to affected region within 28 days before enrollment to study
* Known diagnosis of osteosarcoma or brown tumor of bone
* Known history of second malignancy within the past 5 years, except for basal cell carcinoma or cervical carcinoma in situ
* Concurrent treatment with bisphosphonates, calcitonin, or interferon.

Other criteria also apply.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Overall Officials

**Official 1:**

**Affiliation:** Amgen

**Name:** MD

**Role:** STUDY_DIRECTOR

### References Module

#### References

**Citation:** Branstetter DG, Nelson SD, Manivel JC, Blay JY, Chawla S, Thomas DM, Jun S, Jacobs I. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012 Aug 15;18(16):4415-24. doi: 10.1158/1078-0432.CCR-12-0578. Epub 2012 Jun 18.

**PMID:** 22711702

**Citation:** Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, Roudier M, Smith J, Ye Z, Sohn W, Dansey R, Jun S. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010 Mar;11(3):275-80. doi: 10.1016/S1470-2045(10)70010-3. Epub 2010 Feb 10.

**PMID:** 20149736

**Citation:** 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

#### See Also Links

**Label:** AmgenTrials clinical trials website

**URL:** http://www.amgentrials.com

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009369

- Term: Neoplasms

- ID: D000009372

- Term: Neoplasms, Connective Tissue

- ID: D000018204

- Term: Neoplasms, Connective and Soft Tissue

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000001847

- Term: Bone Diseases

- ID: D000009140

- Term: Musculoskeletal Diseases

- ID: D000018213

- Term: Neoplasms, Bone Tissue

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC05

- Name: Musculoskeletal Diseases

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M14850

- Name: Recurrence

- Relevance: LOW

- As Found: Unknown

- ID: M5138

- Name: Bone Neoplasms

- Relevance: HIGH

- As Found: Tumor of Bone

- ID: M8982

- Name: Giant Cell Tumors

- Relevance: HIGH

- As Found: Giant Cell Tumor

- ID: M20358

- Name: Giant Cell Tumor of Bone

- Relevance: HIGH

- As Found: Giant Cell Tumor of Bone

- ID: M12317

- Name: Neoplasms, Connective Tissue

- Relevance: LOW

- As Found: Unknown

- ID: M20350

- Name: Neoplasms, Connective and Soft Tissue

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M5126

- Name: Bone Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12097

- Name: Musculoskeletal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M20359

- Name: Neoplasms, Bone Tissue

- Relevance: LOW

- As Found: Unknown

- ID: T2489

- Name: Giant Cell Tumor of Bone

- Relevance: HIGH

- As Found: Giant Cell Tumor of Bone

### Condition Browse Module - Meshes

- ID: D000005870

- Term: Giant Cell Tumors

- ID: D000001859

- Term: Bone Neoplasms

- ID: D000018212

- Term: Giant Cell Tumor of Bone

### Intervention Browse Module - Ancestors

- ID: D000014815

- Term: Vitamins

- ID: D000018977

- Term: Micronutrients

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000077264

- Term: Calcium-Regulating Hormones and Agents

- ID: D000050071

- Term: Bone Density Conservation Agents

### Intervention Browse Module - Browse Branches

- Abbrev: BDCA

- Name: Bone Density Conservation Agents

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Vi

- Name: Vitamins

### Intervention Browse Module - Browse Leaves

- ID: M17550

- Name: Vitamin D

- Relevance: HIGH

- As Found: Ultrasound

- ID: M6003

- Name: Cholecalciferol

- Relevance: LOW

- As Found: Unknown

- ID: M5381

- Name: Calcium

- Relevance: HIGH

- As Found: Radiation

- ID: M17558

- Name: Vitamins

- Relevance: LOW

- As Found: Unknown

- ID: M5398

- Name: Calcium, Dietary

- Relevance: LOW

- As Found: Unknown

- ID: M417

- Name: Denosumab

- Relevance: HIGH

- As Found: 0.05

- ID: M21009

- Name: Micronutrients

- Relevance: LOW

- As Found: Unknown

- ID: M16885

- Name: Trace Elements

- Relevance: LOW

- As Found: Unknown

- ID: M9789

- Name: Hormones

- Relevance: LOW

- As Found: Unknown

- ID: T442

- Name: Cholecalciferol

- Relevance: LOW

- As Found: Unknown

- ID: T479

- Name: Vitamin D3

- Relevance: LOW

- As Found: Unknown

- ID: T440

- Name: Calciferol

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000014807

- Term: Vitamin D

- ID: D000069448

- Term: Denosumab

- ID: D000002118

- Term: Calcium

### Misc Info Module

#### Removed Countries

- Country: Australia

- Country: France

- Country: United States

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

**Description:** The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency.

#### Event Groups

**Group ID:** EG000

**Title:** Denosumab 120 mg Q4W

**Description:** Participants received a dose loading regimen of 3 subcutaneous injections of denosumab 120 mg every week for 3 weeks (study Days 1, 8, and 15), followed by a week of rest, and then 120 mg denosumab once every 4 weeks (Q4W) from Day 29.

**ID:** EG000

**Other Num Affected:** 25

**Other Num at Risk:** 37

**Serious Number Affected:** 5

**Serious Number At Risk:** 37

**Title:** Denosumab 120 mg Q4W

**Frequency Threshold:** 5

#### Other Events

**Term:** Constipation

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA 11.0

**Term:** Diarrhoea

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA 11.0

**Term:** Nausea

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA 11.0

**Term:** Asthenia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** MedDRA 11.0

**Term:** Fatigue

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** MedDRA 11.0

**Term:** Bronchitis

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA 11.0

**Term:** Influenza

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA 11.0

**Term:** Nasopharyngitis

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA 11.0

**Term:** Upper respiratory tract infection

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA 11.0

**Term:** Anorexia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Metabolism and nutrition disorders

**Source Vocabulary:** MedDRA 11.0

**Term:** Hypocalcaemia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Metabolism and nutrition disorders

**Source Vocabulary:** MedDRA 11.0

**Term:** Hypophosphataemia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Metabolism and nutrition disorders

**Source Vocabulary:** MedDRA 11.0

**Term:** Arthralgia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA 11.0

**Term:** Back pain

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA 11.0

**Term:** Muscle spasms

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA 11.0

**Term:** Musculoskeletal pain

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA 11.0

**Term:** Pain in extremity

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA 11.0

**Term:** Dizziness

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA 11.0

**Term:** Headache

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA 11.0

**Term:** Cough

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Respiratory, thoracic and mediastinal disorders

**Source Vocabulary:** MedDRA 11.0

#### Serious Events

**Term:** Nausea

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA 11.0

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 37

**Term:** Lower respiratory tract infection

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA 11.0

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 37

**Term:** Pneumonia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA 11.0

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 37

**Term:** Ankle fracture

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Injury, poisoning and procedural complications

**Source Vocabulary:** MedDRA 11.0

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 37

**Term:** Back pain

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA 11.0

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 37

**Term:** Metastases to lung

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps)

**Source Vocabulary:** MedDRA 11.0

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 37

**Term:** Depression

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Psychiatric disorders

**Source Vocabulary:** MedDRA 11.0

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 37

**Term:** Acute respiratory distress syndrome

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Respiratory, thoracic and mediastinal disorders

**Source Vocabulary:** MedDRA 11.0

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 37

**Term:** Dyspnoea

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Respiratory, thoracic and mediastinal disorders

**Source Vocabulary:** MedDRA 11.0

##### Stats

**Group ID:** EG000

**Num Affected:** 2

**Num At Risk:** 37

**Time Frame:** up to 1 year 6 months

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 37

**Units:** Participants

### Group

**ID:** BG000

**Title:** Denosumab

**Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason.

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 12.3

**Value:** 33.9

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 20

**Category Title:** Female

#### Measurement

**Group ID:** BG000

**Value:** 17

**Category Title:** Male

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 27

**Class Title:** White or Caucasian

#### Measurement

**Group ID:** BG000

**Value:** 2

**Class Title:** Black or African American

#### Measurement

**Group ID:** BG000

**Value:** 5

**Class Title:** Hispanic or Latino

#### Measurement

**Group ID:** BG000

**Value:** 3

**Class Title:** Asian

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 13

**Class Title:** Primary unresectable

#### Measurement

**Group ID:** BG000

**Value:** 18

**Class Title:** Recurrent unresectable

#### Measurement

**Group ID:** BG000

**Value:** 6

**Class Title:** Recurrent resectable

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 13

**Class Title:** 0 - Fully Active

#### Measurement

**Group ID:** BG000

**Value:** 21

**Class Title:** 1 - Restricted but ambulatory

#### Measurement

**Group ID:** BG000

**Value:** 1

**Class Title:** 2 - Ambulatory but unable to work

#### Measurement

**Group ID:** BG000

**Value:** 0

**Class Title:** 3 - Limited selfcare, confined to bed >50% daytime

#### Measurement

**Group ID:** BG000

**Value:** 0

**Class Title:** 4 - Completely disabled

#### Measurement

**Group ID:** BG000

**Value:** 2

**Class Title:** Missing

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 16.1

**Value:** 28.7

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 8

**Class Title:** Lower extremities

#### Measurement

**Group ID:** BG000

**Value:** 5

**Class Title:** Upper extremities

#### Measurement

**Group ID:** BG000

**Value:** 9

**Class Title:** Pelvis

#### Measurement

**Group ID:** BG000

**Value:** 3

**Class Title:** Spine

#### Measurement

**Group ID:** BG000

**Value:** 9

**Class Title:** Pulmonary disease

#### Measurement

**Group ID:** BG000

**Value:** 1

**Class Title:** Dorsal vertebrae

#### Measurement

**Group ID:** BG000

**Value:** 1

**Class Title:** Pelvic region

#### Measurement

**Group ID:** BG000

**Value:** 1

**Class Title:** Missing

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Age, Continuous
**Unit of Measure:** years
### Measure 2
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
### Measure 3
**Parameter Type:** NUMBER
**Title:** Race/Ethnicity, Customized
**Unit of Measure:** participants
### Measure 4
**Parameter Type:** NUMBER
**Title:** Giant Cell Tumor Disease Type
**Unit of Measure:** participants
### Measure 5
**Description:** 0: Fully active, able to carry on all pre-disease performance without restriction;

1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work;
2. Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours;
3. Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours;
4. Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair.
**Parameter Type:** NUMBER
**Title:** Eastern Cooperative Oncology Group (ECOG) Performance Status
**Unit of Measure:** participants
### Measure 6
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Percent of giant cells in tumor on pre-treatment biopsy
**Unit of Measure:** percentage of giant cells in tumor
### Measure 7
**Parameter Type:** NUMBER
**Title:** Location of target lesion
**Unit of Measure:** participants
## Results Section - More Information Module
### Certain Agreement
**Other Details:** The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results aftercompletion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
**Restriction Type:** OTHER
**Restrictive Agreement:** True
### Point of Contact
**Organization:** Amgen Inc.
**Phone:** 866-572-6436
**Title:** Study Director
## Results Section - Outcome Measures Module
### Outcome Measure 1
### Outcome Measure 2
### Outcome Measure 3
### Outcome Measure 4
### Outcome Measure 5
### Outcome Measure 6
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 69.7
- **Spread:** 
- **Upper Limit:** 95.2
- **Value:** 85.7
**Title:** 
#### Outcome Measure 2
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -79.6
- **Spread:** 
- **Upper Limit:** -15.0
- **Value:** -70.9
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -85.7
- **Spread:** 
- **Upper Limit:** -42.9
- **Value:** -77.0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -84.2
- **Spread:** 
- **Upper Limit:** -36.0
- **Value:** -60.0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -79.3
- **Spread:** 
- **Upper Limit:** -37.1
- **Value:** -59.5
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -80.1
- **Spread:** 
- **Upper Limit:** -19.1
- **Value:** -64.5
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -76.2
- **Spread:** 
- **Upper Limit:** 3.6
- **Value:** -56.4
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -78.4
- **Spread:** 
- **Upper Limit:** -22.8
- **Value:** -52.8
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -83.8
- **Spread:** 
- **Upper Limit:** 22.0
- **Value:** -35.0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -83.4
- **Spread:** 
- **Upper Limit:** -41.4
- **Value:** -71.1
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -78.1
- **Spread:** 
- **Upper Limit:** -22.4
- **Value:** -57.3
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -81.8
- **Spread:** 
- **Upper Limit:** -47.5
- **Value:** -59.1
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -74.0
- **Spread:** 
- **Upper Limit:** -0.9
- **Value:** -59.0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -81.5
- **Spread:** 
- **Upper Limit:** -29.3
- **Value:** -49.0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -78.4
- **Spread:** 
- **Upper Limit:** -21.9
- **Value:** -65.1
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -92.5
- **Spread:** 
- **Upper Limit:** 23.1
- **Value:** -59.2
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -79.6
- **Spread:** 
- **Upper Limit:** 33.2
- **Value:** -69.2
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -88.8
- **Spread:** 
- **Upper Limit:** -13.4
- **Value:** -64.2
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -47.5
- **Spread:** 
- **Upper Limit:** -47.5
- **Value:** -47.5
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -86.8
- **Spread:** 
- **Upper Limit:** -66.7
- **Value:** -76.8
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -53.8
- **Spread:** 
- **Upper Limit:** 27.1
- **Value:** -13.3
**Title:** 
#### Outcome Measure 3
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -85.2
- **Spread:** 
- **Upper Limit:** -71.2
- **Value:** -78.9
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -87.9
- **Spread:** 
- **Upper Limit:** -66.1
- **Value:** -79.8
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -85.7
- **Spread:** 
- **Upper Limit:** -71.3
- **Value:** -80.4
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -85.2
- **Spread:** 
- **Upper Limit:** -70.4
- **Value:** -82.6
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -87.0
- **Spread:** 
- **Upper Limit:** -66.4
- **Value:** -82.0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -86.5
- **Spread:** 
- **Upper Limit:** -69.2
- **Value:** -79.5
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -85.2
- **Spread:** 
- **Upper Limit:** -60.3
- **Value:** -82.8
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -83.2
- **Spread:** 
- **Upper Limit:** -59.0
- **Value:** -74.8
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -87.0
- **Spread:** 
- **Upper Limit:** -69.6
- **Value:** -82.4
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -89.6
- **Spread:** 
- **Upper Limit:** -58.5
- **Value:** -86.1
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -86.4
- **Spread:** 
- **Upper Limit:** -70.0
- **Value:** -79.6
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -90.0
- **Spread:** 
- **Upper Limit:** -76.7
- **Value:** -82.0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -89.8
- **Spread:** 
- **Upper Limit:** -84.2
- **Value:** -87.3
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -87.7
- **Spread:** 
- **Upper Limit:** -85.2
- **Value:** -86.2
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -88.3
- **Spread:** 
- **Upper Limit:** -83.0
- **Value:** -84.9
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -87.0
- **Spread:** 
- **Upper Limit:** -77.5
- **Value:** -83.5
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -86.9
- **Spread:** 
- **Upper Limit:** -80.0
- **Value:** -84.2
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -85.2
- **Spread:** 
- **Upper Limit:** -78.5
- **Value:** -81.9
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -87.5
- **Spread:** 
- **Upper Limit:** -80.9
- **Value:** -84.2
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** -89.6
- **Spread:** 
- **Upper Limit:** -80.3
- **Value:** -84.9
**Title:** 
#### Outcome Measure 4
**Class:**
##### Category
**Measurements:**
- **Comment:** Below the lower limit of quantification
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** NA
- **Upper Limit:** 
- **Value:** NA
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 24100
- **Upper Limit:** 
- **Value:** 19000
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 27300
- **Upper Limit:** 
- **Value:** 31600
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 20600
- **Upper Limit:** 
- **Value:** 36400
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 17300
- **Upper Limit:** 
- **Value:** 27500
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 12400
- **Upper Limit:** 
- **Value:** 23300
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 9700
- **Upper Limit:** 
- **Value:** 19900
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 8900
- **Upper Limit:** 
- **Value:** 21400
**Title:** 
#### Outcome Measure 5
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 33
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 5
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 2
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 3
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 5
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 10
**Title:** 
#### Outcome Measure 6
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
**Title:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** A treatment response was defined for participants with tissue samples obtained and measured by histopathology as: • at least 90% elimination of giant cells relative to Baseline, or • complete elimination of giant cells in cases where giant cells represent \< 5% of tumor cells. A response was defined for participants who have only radiographs (histopathology not available) as lack of progression of the target lesion at week 25 by radiographic measurements compared with Baseline. For participants with both a core biopsy and resected tissue obtained, the sample closest to week 25 was used in the analysis.
**Dispersion Type:** 95% Confidence Interval
**Parameter Type:** NUMBER
**Population Description:** The efficacy analysis set included participants with a Baseline histology assessment and at least 1 postdose histology assessment from weeks 5-25; or a Baseline radiology assessment and at least 1 postdose radiology assessment from weeks 5-25. Evaluable participants had to be on study for at least 28 days after administration of the first dose.
**Reporting Status:** POSTED
**Time Frame:** From enrollment until 25 weeks
**Title:** Percentage of Participants With Giant Cell Tumor Response
**Type:** PRIMARY
**Unit of Measure:** percentage of participants
##### Group
**Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason.
**ID:** OG000
**Title:** Denosumab
#### Outcome Measure 2
**Description:** Urinary N-telopeptide (of type 1 collagen) corrected for urine creatinine (uNTX/Cr) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in uNTX/Cr was measured over time.
**Dispersion Type:** Inter-Quartile Range
**Parameter Type:** MEDIAN
**Population Description:** Efficacy Analysis Set with available data at each time point (n).
**Reporting Status:** POSTED
**Time Frame:** Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81
**Title:** Percent Change From Baseline in Urinary N-telopeptide Corrected for Urine Creatinine
**Type:** SECONDARY
**Unit of Measure:** percent change
##### Group
**Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason.
**ID:** OG000
**Title:** Denosumab
#### Outcome Measure 3
**Description:** Serum C-terminus peptide (of type 1 collagen; CTX1) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in CTX was measured over time.
**Dispersion Type:** Inter-Quartile Range
**Parameter Type:** MEDIAN
**Population Description:** Efficacy Analysis Set with available data at each time point (n).
**Reporting Status:** POSTED
**Time Frame:** Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81
**Title:** Percent Change From Baseline in Serum C-terminus Peptide (of Type 1 Collagen)
**Type:** SECONDARY
**Unit of Measure:** percent change
##### Group
**Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason.
**ID:** OG000
**Title:** Denosumab
#### Outcome Measure 4
**Description:** Serum concentrations of denosumab were measured by a validated conventional sandwich enzyme-linked immunosorbent assay (ELISA).
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Population Description:** The pharmacokinetics analysis set included participants who received at least 1 dose of denosumab and for whom at least 1 serum denosumab trough concentration was available. 'n' indicates the number of participants with available data at each time point.
**Reporting Status:** POSTED
**Time Frame:** Blood samples were collected on Days 1 (baseline), 8, 15 and Weeks 5 (Day 29), 9, 13, 25, and 49.
**Title:** Serum Denosumab Trough Concentrations
**Type:** SECONDARY
**Unit of Measure:** ng/mL
##### Group
**Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason.
**ID:** OG000
**Title:** Denosumab
#### Outcome Measure 5
**Description:** An adverse event is defined as an undesirable medical occurrence (e.g., sign, symptom, or diagnosis) or worsening of a pre-existing medical condition. A serious adverse event (SAE) is defined by regulatory authorities as one that • is fatal • is life threatening (places the participant at immediate risk of death) • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard. The severity of adverse events was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, version 3.0) based on the following general guideline: Grade 1: Mild AE Grade 2: Moderate AE Grade 3: Severe AE Grade 4: Life-threatening or disabling AE Grade 5: Death related to AE. AEs were assessed by the Investigator for relatedness to study drug.
**Parameter Type:** NUMBER
**Population Description:** All participants who received at least 1 dose of denosumab.
**Reporting Status:** POSTED
**Time Frame:** From the first dose of study drug until the data cut-off date of April 7 2008; a maximum of 18 months
**Title:** Number of Participants With Adverse Events (AEs)
**Type:** SECONDARY
**Unit of Measure:** participants
##### Group
**Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason.
**ID:** OG000
**Title:** Denosumab
#### Outcome Measure 6
**Description:** Validated immunoassays were used to test for the presence of anti-denosumab antibodies throughout the study.
**Parameter Type:** NUMBER
**Population Description:** Participants who received at least 1 dose of denosumab and had at least 1 anti-denosumab antibody sample.
**Reporting Status:** POSTED
**Time Frame:** From enrollment until the data cut-off date of April 7 2008; a maximum time of 18 months.
**Title:** Number of Participants With Anti-Denosumab Antibodies
**Type:** SECONDARY
**Unit of Measure:** participants
##### Group
**Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason.
**ID:** OG000
**Title:** Denosumab
### Participant Flow Module
#### Group
**Description:** Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason.
**ID:** FG000
**Title:** Denosumab
#### Period
**Title:** Overall Study
##### Withdraw
**Type:** Ongoing in study
###### Reason
**Group ID:** FG000
**Number of Subjects:** 26
##### Withdraw
**Type:** Disease progression
###### Reason
**Group ID:** FG000
**Number of Subjects:** 2
##### Withdraw
**Type:** Withdrawal by Subject
###### Reason
**Group ID:** FG000
**Number of Subjects:** 1
##### Withdraw
**Type:** Physician Decision
###### Reason
**Group ID:** FG000
**Number of Subjects:** 1
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 37
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 7
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 30
**Recruitment Details:** First patient enrolled 10 July 2006; Last patient enrolled 25 January 2008. Results data are reported as of the data cut-off date of 07 April 2008.
**Has Results:** True